anno_start	anno_end	anno_text	entity_type	sentence	section
19	34	T cell receptor	protein_type	Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity	TITLE
66	73	insulin	chemical	Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity	TITLE
46	69	T cell antigen receptor	complex_assembly	However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear.	ABSTRACT
71	74	TCR	complex_assembly	However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear.	ABSTRACT
108	150	peptide–major histocompatibility complexes	complex_assembly	However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear.	ABSTRACT
152	156	pMHC	complex_assembly	However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear.	ABSTRACT
49	54	human	species	Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I–restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides.	ABSTRACT
56	69	preproinsulin	protein	Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I–restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides.	ABSTRACT
80	83	MHC	complex_assembly	Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I–restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides.	ABSTRACT
29	39	structures	evidence	We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide.	ABSTRACT
47	54	1E6 TCR	complex_assembly	We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide.	ABSTRACT
55	63	bound to	protein_state	We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide.	ABSTRACT
66	89	altered peptide ligands	chemical	We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide.	ABSTRACT
20	30	structures	evidence	Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key–like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot.	ABSTRACT
149	156	1E6 TCR	complex_assembly	Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key–like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot.	ABSTRACT
30	37	1E6 TCR	complex_assembly	Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand.	ABSTRACT
60	94	antipathogen-like binding affinity	evidence	Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand.	ABSTRACT
150	174	major histocompatibility	complex_assembly	T cells perform an essential role in adaptive immunity by interrogating the host proteome for anomalies, classically by recognizing peptides bound in major histocompatibility (MHC) molecules at the cell surface.	INTRO
176	179	MHC	complex_assembly	T cells perform an essential role in adaptive immunity by interrogating the host proteome for anomalies, classically by recognizing peptides bound in major histocompatibility (MHC) molecules at the cell surface.	INTRO
64	79	highly variable	protein_state	Recent data supports the notion that, to perform this role, the highly variable αβ T cell antigen receptor (TCR) must be able to recognize thousands, if not millions, of different peptide ligands.	INTRO
80	106	αβ T cell antigen receptor	complex_assembly	Recent data supports the notion that, to perform this role, the highly variable αβ T cell antigen receptor (TCR) must be able to recognize thousands, if not millions, of different peptide ligands.	INTRO
108	111	TCR	complex_assembly	Recent data supports the notion that, to perform this role, the highly variable αβ T cell antigen receptor (TCR) must be able to recognize thousands, if not millions, of different peptide ligands.	INTRO
69	73	TCRs	complex_assembly	This ability is required to enable the estimated 25 million distinct TCRs expressed in humans to provide effective immune coverage against all possible foreign peptide antigens.	INTRO
87	93	humans	species	This ability is required to enable the estimated 25 million distinct TCRs expressed in humans to provide effective immune coverage against all possible foreign peptide antigens.	INTRO
29	33	TCRs	complex_assembly	Several mechanisms, by which TCRs could bind to a large number of different peptide-MHC (pMHC), have been proposed.	INTRO
76	87	peptide-MHC	complex_assembly	Several mechanisms, by which TCRs could bind to a large number of different peptide-MHC (pMHC), have been proposed.	INTRO
89	93	pMHC	complex_assembly	Several mechanisms, by which TCRs could bind to a large number of different peptide-MHC (pMHC), have been proposed.	INTRO
0	10	Structures	evidence	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
14	23	unligated	protein_state	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
28	35	ligated	protein_state	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
36	40	TCRs	complex_assembly	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
61	64	TCR	complex_assembly	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
65	99	complementarity determining region	structure_element	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
101	104	CDR	structure_element	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
106	111	loops	structure_element	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
178	182	loop	structure_element	Structures of unligated and ligated TCRs have shown that the TCR complementarity determining region (CDR) loops can be flexible, perhaps enabling peptide binding using different loop conformations.	INTRO
5	8	MHC	complex_assembly	Both MHC and peptide have also been shown to undergo structural changes upon TCR binding, mediating an induced fit between the TCR and pMHC.	INTRO
13	20	peptide	chemical	Both MHC and peptide have also been shown to undergo structural changes upon TCR binding, mediating an induced fit between the TCR and pMHC.	INTRO
77	80	TCR	complex_assembly	Both MHC and peptide have also been shown to undergo structural changes upon TCR binding, mediating an induced fit between the TCR and pMHC.	INTRO
127	130	TCR	complex_assembly	Both MHC and peptide have also been shown to undergo structural changes upon TCR binding, mediating an induced fit between the TCR and pMHC.	INTRO
135	139	pMHC	complex_assembly	Both MHC and peptide have also been shown to undergo structural changes upon TCR binding, mediating an induced fit between the TCR and pMHC.	INTRO
29	35	murine	taxonomy_domain	Other studies, mainly in the murine system, have demonstrated that the same TCR can interact with different pMHCs using a common or divergent modality.	INTRO
76	79	TCR	complex_assembly	Other studies, mainly in the murine system, have demonstrated that the same TCR can interact with different pMHCs using a common or divergent modality.	INTRO
108	113	pMHCs	complex_assembly	Other studies, mainly in the murine system, have demonstrated that the same TCR can interact with different pMHCs using a common or divergent modality.	INTRO
24	30	murine	taxonomy_domain	Recent studies in model murine systems demonstrate that TCR cross-reactivity can be governed by recognition of a conserved region in the peptide that allows tolerance of peptide sequence variation outside of this hotspot.	INTRO
56	59	TCR	complex_assembly	Recent studies in model murine systems demonstrate that TCR cross-reactivity can be governed by recognition of a conserved region in the peptide that allows tolerance of peptide sequence variation outside of this hotspot.	INTRO
34	39	human	species	We recently reported that the 1E6 human CD8+ T cell clone — which mediates the destruction of β cells through the recognition of a major, HLA-A*0201–restricted, preproinsulin signal peptide (ALWGPDPAAA15–24) — can recognize upwards of 1 million different peptides.	INTRO
138	148	HLA-A*0201	protein	We recently reported that the 1E6 human CD8+ T cell clone — which mediates the destruction of β cells through the recognition of a major, HLA-A*0201–restricted, preproinsulin signal peptide (ALWGPDPAAA15–24) — can recognize upwards of 1 million different peptides.	INTRO
161	174	preproinsulin	protein	We recently reported that the 1E6 human CD8+ T cell clone — which mediates the destruction of β cells through the recognition of a major, HLA-A*0201–restricted, preproinsulin signal peptide (ALWGPDPAAA15–24) — can recognize upwards of 1 million different peptides.	INTRO
175	189	signal peptide	structure_element	We recently reported that the 1E6 human CD8+ T cell clone — which mediates the destruction of β cells through the recognition of a major, HLA-A*0201–restricted, preproinsulin signal peptide (ALWGPDPAAA15–24) — can recognize upwards of 1 million different peptides.	INTRO
191	206	ALWGPDPAAA15–24	chemical	We recently reported that the 1E6 human CD8+ T cell clone — which mediates the destruction of β cells through the recognition of a major, HLA-A*0201–restricted, preproinsulin signal peptide (ALWGPDPAAA15–24) — can recognize upwards of 1 million different peptides.	INTRO
28	49	HLA-A*0201–ALWGPDPAAA	complex_assembly	CD8+ T cells that recognize HLA-A*0201–ALWGPDPAAA have been shown to populate insulitic lesions in patients with type 1 diabetes (T1D).	INTRO
25	28	TCR	complex_assembly	We demonstrated that the TCR from the 1E6 T cell clone bound to HLA-A*0201–ALWGPDPAAA using a limited footprint and very weak binding affinity.	INTRO
55	63	bound to	protein_state	We demonstrated that the TCR from the 1E6 T cell clone bound to HLA-A*0201–ALWGPDPAAA using a limited footprint and very weak binding affinity.	INTRO
64	85	HLA-A*0201–ALWGPDPAAA	complex_assembly	We demonstrated that the TCR from the 1E6 T cell clone bound to HLA-A*0201–ALWGPDPAAA using a limited footprint and very weak binding affinity.	INTRO
126	142	binding affinity	evidence	We demonstrated that the TCR from the 1E6 T cell clone bound to HLA-A*0201–ALWGPDPAAA using a limited footprint and very weak binding affinity.	INTRO
86	91	human	species	This first experimental evidence of a high level of CD8+ T cell cross-reactivity in a human autoimmune disease system hinted toward molecular mimicry by a more potent pathogenic peptide as a potential mechanism leading to β cell destruction.	INTRO
9	15	solved	experimental_method	Here, we solved the structure of the 1E6 TCR with 7 altered peptide ligands (APLs) determined by our previously published combinatorial peptide library (CPL) screening, 2 of which mapped within human pathogens.	INTRO
20	29	structure	evidence	Here, we solved the structure of the 1E6 TCR with 7 altered peptide ligands (APLs) determined by our previously published combinatorial peptide library (CPL) screening, 2 of which mapped within human pathogens.	INTRO
37	44	1E6 TCR	complex_assembly	Here, we solved the structure of the 1E6 TCR with 7 altered peptide ligands (APLs) determined by our previously published combinatorial peptide library (CPL) screening, 2 of which mapped within human pathogens.	INTRO
52	75	altered peptide ligands	chemical	Here, we solved the structure of the 1E6 TCR with 7 altered peptide ligands (APLs) determined by our previously published combinatorial peptide library (CPL) screening, 2 of which mapped within human pathogens.	INTRO
77	81	APLs	chemical	Here, we solved the structure of the 1E6 TCR with 7 altered peptide ligands (APLs) determined by our previously published combinatorial peptide library (CPL) screening, 2 of which mapped within human pathogens.	INTRO
122	167	combinatorial peptide library (CPL) screening	experimental_method	Here, we solved the structure of the 1E6 TCR with 7 altered peptide ligands (APLs) determined by our previously published combinatorial peptide library (CPL) screening, 2 of which mapped within human pathogens.	INTRO
194	199	human	species	Here, we solved the structure of the 1E6 TCR with 7 altered peptide ligands (APLs) determined by our previously published combinatorial peptide library (CPL) screening, 2 of which mapped within human pathogens.	INTRO
6	10	APLs	chemical	These APLs differed from the natural preproinsulin peptide by up to 7 of 10 residues.	INTRO
37	50	preproinsulin	protein	These APLs differed from the natural preproinsulin peptide by up to 7 of 10 residues.	INTRO
8	14	solved	experimental_method	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
19	28	structure	evidence	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
37	46	unligated	protein_state	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
47	50	APL	chemical	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
161	194	cellular and biophysical analysis	experimental_method	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
228	231	APL	chemical	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
333	346	preproinsulin	protein	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
356	361	human	species	We also solved the structure of each unligated APL to investigate whether structural changes occurred before or after binding — which, combined with an in-depth cellular and biophysical analysis of the 1E6 interaction with each APL, demonstrated the molecular mechanism mediating the high level of cross-reactivity exhibited by this preproinsulin-reactive human CD8+ T cell clone.	INTRO
32	36	APLs	chemical	The 1E6 T cell clone recognizes APLs across a large dynamic range.	RESULTS
166	179	preproinsulin	protein	We have previously demonstrated that the 1E6 T cell clone can recognize over 1 million different peptides with a potency comparable with, or better than, the cognate preproinsulin peptide ALWGPDPAAA.	RESULTS
188	198	ALWGPDPAAA	chemical	We have previously demonstrated that the 1E6 T cell clone can recognize over 1 million different peptides with a potency comparable with, or better than, the cognate preproinsulin peptide ALWGPDPAAA.	RESULTS
57	61	APLs	chemical	From this large functional scan, we selected 7 different APLs that activated the 1E6 T cell clone across a wide (4-log) functional range (Table 1).	RESULTS
23	33	MVWGPDPLYV	chemical	Two of these peptides, MVWGPDPLYV and RQFGPDWIVA (bold text signifies amino acids that are different from the index preproinsulin–derived sequence), are contained within the proteomes of the human pathogens Bacteroides fragilis/thetaiotaomicron and Clostridium asparagiforme, respectively.	RESULTS
38	48	RQFGPDWIVA	chemical	Two of these peptides, MVWGPDPLYV and RQFGPDWIVA (bold text signifies amino acids that are different from the index preproinsulin–derived sequence), are contained within the proteomes of the human pathogens Bacteroides fragilis/thetaiotaomicron and Clostridium asparagiforme, respectively.	RESULTS
116	129	preproinsulin	protein	Two of these peptides, MVWGPDPLYV and RQFGPDWIVA (bold text signifies amino acids that are different from the index preproinsulin–derived sequence), are contained within the proteomes of the human pathogens Bacteroides fragilis/thetaiotaomicron and Clostridium asparagiforme, respectively.	RESULTS
191	196	human	species	Two of these peptides, MVWGPDPLYV and RQFGPDWIVA (bold text signifies amino acids that are different from the index preproinsulin–derived sequence), are contained within the proteomes of the human pathogens Bacteroides fragilis/thetaiotaomicron and Clostridium asparagiforme, respectively.	RESULTS
207	244	Bacteroides fragilis/thetaiotaomicron	species	Two of these peptides, MVWGPDPLYV and RQFGPDWIVA (bold text signifies amino acids that are different from the index preproinsulin–derived sequence), are contained within the proteomes of the human pathogens Bacteroides fragilis/thetaiotaomicron and Clostridium asparagiforme, respectively.	RESULTS
249	274	Clostridium asparagiforme	species	Two of these peptides, MVWGPDPLYV and RQFGPDWIVA (bold text signifies amino acids that are different from the index preproinsulin–derived sequence), are contained within the proteomes of the human pathogens Bacteroides fragilis/thetaiotaomicron and Clostridium asparagiforme, respectively.	RESULTS
0	30	Competitive functional testing	experimental_method	Competitive functional testing revealed that the preproinsulin-derived sequence ALWGPDPAAA was one of the least potent targets for 1E6, with only the MVWGPDPLYV and YLGGPDFPTI demonstrating a similar low-activity profile in MIP-1β secretion and target killing assays (Figure 1, A and B).	RESULTS
49	62	preproinsulin	protein	Competitive functional testing revealed that the preproinsulin-derived sequence ALWGPDPAAA was one of the least potent targets for 1E6, with only the MVWGPDPLYV and YLGGPDFPTI demonstrating a similar low-activity profile in MIP-1β secretion and target killing assays (Figure 1, A and B).	RESULTS
80	90	ALWGPDPAAA	chemical	Competitive functional testing revealed that the preproinsulin-derived sequence ALWGPDPAAA was one of the least potent targets for 1E6, with only the MVWGPDPLYV and YLGGPDFPTI demonstrating a similar low-activity profile in MIP-1β secretion and target killing assays (Figure 1, A and B).	RESULTS
150	160	MVWGPDPLYV	chemical	Competitive functional testing revealed that the preproinsulin-derived sequence ALWGPDPAAA was one of the least potent targets for 1E6, with only the MVWGPDPLYV and YLGGPDFPTI demonstrating a similar low-activity profile in MIP-1β secretion and target killing assays (Figure 1, A and B).	RESULTS
165	175	YLGGPDFPTI	chemical	Competitive functional testing revealed that the preproinsulin-derived sequence ALWGPDPAAA was one of the least potent targets for 1E6, with only the MVWGPDPLYV and YLGGPDFPTI demonstrating a similar low-activity profile in MIP-1β secretion and target killing assays (Figure 1, A and B).	RESULTS
224	230	MIP-1β	protein	Competitive functional testing revealed that the preproinsulin-derived sequence ALWGPDPAAA was one of the least potent targets for 1E6, with only the MVWGPDPLYV and YLGGPDFPTI demonstrating a similar low-activity profile in MIP-1β secretion and target killing assays (Figure 1, A and B).	RESULTS
4	14	RQFGPDWIVA	chemical	The RQFGPDWIVA sequence (present in C. asparagiforme) activated the 1E6 T cell with around 1 log–greater potency compared with ALWGPDPAAA.	RESULTS
36	52	C. asparagiforme	species	The RQFGPDWIVA sequence (present in C. asparagiforme) activated the 1E6 T cell with around 1 log–greater potency compared with ALWGPDPAAA.	RESULTS
127	137	ALWGPDPAAA	chemical	The RQFGPDWIVA sequence (present in C. asparagiforme) activated the 1E6 T cell with around 1 log–greater potency compared with ALWGPDPAAA.	RESULTS
38	48	RQFGPDFPTI	chemical	At the other end of the spectrum, the RQFGPDFPTI peptide stimulated MIP-1β release and killing by 1E6 at an exogenous peptide concentration 2–3 logs lower compared with ALWGPDPAAA.	RESULTS
68	74	MIP-1β	protein	At the other end of the spectrum, the RQFGPDFPTI peptide stimulated MIP-1β release and killing by 1E6 at an exogenous peptide concentration 2–3 logs lower compared with ALWGPDPAAA.	RESULTS
169	179	ALWGPDPAAA	chemical	At the other end of the spectrum, the RQFGPDFPTI peptide stimulated MIP-1β release and killing by 1E6 at an exogenous peptide concentration 2–3 logs lower compared with ALWGPDPAAA.	RESULTS
55	59	pMHC	complex_assembly	The pattern of peptide potency was closely mirrored by pMHC tetramer staining experiments (Figure 1C and plots shown in Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI85679DS1).	RESULTS
60	77	tetramer staining	experimental_method	The pattern of peptide potency was closely mirrored by pMHC tetramer staining experiments (Figure 1C and plots shown in Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI85679DS1).	RESULTS
10	23	A2-RQFGPDFPTI	chemical	Here, the A2-RQFGPDFPTI tetramer stained 1E6 with the greatest MFI, gradually decreasing to the weakest tetramers: A2-MVWGPDPLYV and -YLGGPDFPTI.	RESULTS
24	32	tetramer	oligomeric_state	Here, the A2-RQFGPDFPTI tetramer stained 1E6 with the greatest MFI, gradually decreasing to the weakest tetramers: A2-MVWGPDPLYV and -YLGGPDFPTI.	RESULTS
104	113	tetramers	oligomeric_state	Here, the A2-RQFGPDFPTI tetramer stained 1E6 with the greatest MFI, gradually decreasing to the weakest tetramers: A2-MVWGPDPLYV and -YLGGPDFPTI.	RESULTS
115	128	A2-MVWGPDPLYV	chemical	Here, the A2-RQFGPDFPTI tetramer stained 1E6 with the greatest MFI, gradually decreasing to the weakest tetramers: A2-MVWGPDPLYV and -YLGGPDFPTI.	RESULTS
134	144	YLGGPDFPTI	chemical	Here, the A2-RQFGPDFPTI tetramer stained 1E6 with the greatest MFI, gradually decreasing to the weakest tetramers: A2-MVWGPDPLYV and -YLGGPDFPTI.	RESULTS
55	67	thermal melt	experimental_method	To parallel the functional analysis, we also performed thermal melt (Tm) experiments using synchrotron radiation circular dichroism (SRCD) to investigate the stability of each APL (Figure 1D).	RESULTS
69	71	Tm	evidence	To parallel the functional analysis, we also performed thermal melt (Tm) experiments using synchrotron radiation circular dichroism (SRCD) to investigate the stability of each APL (Figure 1D).	RESULTS
91	131	synchrotron radiation circular dichroism	experimental_method	To parallel the functional analysis, we also performed thermal melt (Tm) experiments using synchrotron radiation circular dichroism (SRCD) to investigate the stability of each APL (Figure 1D).	RESULTS
133	137	SRCD	experimental_method	To parallel the functional analysis, we also performed thermal melt (Tm) experiments using synchrotron radiation circular dichroism (SRCD) to investigate the stability of each APL (Figure 1D).	RESULTS
176	179	APL	chemical	To parallel the functional analysis, we also performed thermal melt (Tm) experiments using synchrotron radiation circular dichroism (SRCD) to investigate the stability of each APL (Figure 1D).	RESULTS
13	15	Tm	evidence	The range of Tm was between 49.4°C (RQFGPDWIVA) and 60.3°C (YQFGPDFPIA), with an average approximately 55°C, similar to our previous findings.	RESULTS
36	46	RQFGPDWIVA	chemical	The range of Tm was between 49.4°C (RQFGPDWIVA) and 60.3°C (YQFGPDFPIA), with an average approximately 55°C, similar to our previous findings.	RESULTS
60	70	YQFGPDFPIA	chemical	The range of Tm was between 49.4°C (RQFGPDWIVA) and 60.3°C (YQFGPDFPIA), with an average approximately 55°C, similar to our previous findings.	RESULTS
74	91	tetramer staining	experimental_method	This pattern of stability did not correlate with the T cell activation or tetramer staining experiments, indicating that peptide binding to the MHC do not explain ligand potency.	RESULTS
144	147	MHC	complex_assembly	This pattern of stability did not correlate with the T cell activation or tetramer staining experiments, indicating that peptide binding to the MHC do not explain ligand potency.	RESULTS
4	11	1E6 TCR	complex_assembly	The 1E6 TCR can bind peptides with strong antipathogen-like affinities.	RESULTS
65	69	TCRs	complex_assembly	We, and others, have previously demonstrated that antipathogenic TCRs tend to bind with stronger affinity compared with self-reactive TCRs, likely a consequence of the deletion of T cells with high-affinity self-reactive TCR during thymic selection.	RESULTS
97	105	affinity	evidence	We, and others, have previously demonstrated that antipathogenic TCRs tend to bind with stronger affinity compared with self-reactive TCRs, likely a consequence of the deletion of T cells with high-affinity self-reactive TCR during thymic selection.	RESULTS
134	138	TCRs	complex_assembly	We, and others, have previously demonstrated that antipathogenic TCRs tend to bind with stronger affinity compared with self-reactive TCRs, likely a consequence of the deletion of T cells with high-affinity self-reactive TCR during thymic selection.	RESULTS
198	206	affinity	evidence	We, and others, have previously demonstrated that antipathogenic TCRs tend to bind with stronger affinity compared with self-reactive TCRs, likely a consequence of the deletion of T cells with high-affinity self-reactive TCR during thymic selection.	RESULTS
221	224	TCR	complex_assembly	We, and others, have previously demonstrated that antipathogenic TCRs tend to bind with stronger affinity compared with self-reactive TCRs, likely a consequence of the deletion of T cells with high-affinity self-reactive TCR during thymic selection.	RESULTS
35	42	1E6 TCR	complex_assembly	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
43	48	bound	protein_state	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
61	74	preproinsulin	protein	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
84	94	ALWGPDPAAA	chemical	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
113	121	affinity	evidence	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
148	153	human	species	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
174	177	TCR	complex_assembly	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
215	217	KD	evidence	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
228	230	KD	evidence	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
232	260	equilibrium binding constant	evidence	In accordance with this trend, the 1E6 TCR bound the natural preproinsulin peptide, ALWGPDPAAA, with the weakest affinity currently published for a human CD8+ T cell–derived TCR with a biologically relevant ligand (KD > 200 μM; KD, equilibrium binding constant).	RESULTS
0	25	Surface plasmon resonance	experimental_method	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
27	30	SPR	experimental_method	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
48	55	1E6 TCR	complex_assembly	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
56	60	pMHC	complex_assembly	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
83	87	APLs	chemical	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
131	147	binding affinity	evidence	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
164	167	ΔG°	evidence	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
204	208	EC50	evidence	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
325	355	Pearson’s correlation analysis	experimental_method	Surface plasmon resonance (SPR) analysis of the 1E6 TCR–pMHC interaction for all 7 APLs (Figure 2, A–H) demonstrated that stronger binding affinity (represented as ΔG°, kcal/mol) correlated well with the EC50 values (peptide concentration required to reach half-maximal 1E6 T cell killing) for each ligand, demonstrated by a Pearson’s correlation analysis value of 0.8 (P = 0.01) (Figure 2I).	RESULTS
121	131	affinities	evidence	It should be noted that this correlation, although consistent with the T cell killing experiments, uses only approximate affinities calculated for the 2 weakest ligands.	RESULTS
75	95	TCR binding affinity	evidence	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
126	150	1E6 TCR binding affinity	evidence	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
159	172	A2-MVWGPDPLYV	chemical	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
185	187	KD	evidence	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
211	218	1E6 TCR	complex_assembly	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
219	227	bound to	protein_state	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
228	241	A2-RQFGPDFPTI	chemical	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
247	249	KD	evidence	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
278	294	binding affinity	evidence	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
330	334	TCRs	complex_assembly	First, the 1E6 T cell could still functionally respond to peptide when the TCR binding affinity was extremely weak, e.g., the 1E6 TCR binding affinity for the A2-MVWGPDPLYV peptide was KD = ~600 μM. Second, the 1E6 TCR bound to A2-RQFGPDFPTI with KD = 0.5 μM, equivalent to the binding affinity of the very strongest antipathogen TCRs.	RESULTS
11	18	1E6 TCR	complex_assembly	Third, the 1E6 TCR bound to A2-RQFGPDWIVA peptide, within the C. asparagiforme proteome, with approximately 4-fold stronger affinity than A2-ALWGPDPAAA, demonstrating the potential for a pathogen-derived antigen to initiate a response to the self-derived sequence.	RESULTS
19	27	bound to	protein_state	Third, the 1E6 TCR bound to A2-RQFGPDWIVA peptide, within the C. asparagiforme proteome, with approximately 4-fold stronger affinity than A2-ALWGPDPAAA, demonstrating the potential for a pathogen-derived antigen to initiate a response to the self-derived sequence.	RESULTS
28	41	A2-RQFGPDWIVA	chemical	Third, the 1E6 TCR bound to A2-RQFGPDWIVA peptide, within the C. asparagiforme proteome, with approximately 4-fold stronger affinity than A2-ALWGPDPAAA, demonstrating the potential for a pathogen-derived antigen to initiate a response to the self-derived sequence.	RESULTS
62	78	C. asparagiforme	species	Third, the 1E6 TCR bound to A2-RQFGPDWIVA peptide, within the C. asparagiforme proteome, with approximately 4-fold stronger affinity than A2-ALWGPDPAAA, demonstrating the potential for a pathogen-derived antigen to initiate a response to the self-derived sequence.	RESULTS
124	132	affinity	evidence	Third, the 1E6 TCR bound to A2-RQFGPDWIVA peptide, within the C. asparagiforme proteome, with approximately 4-fold stronger affinity than A2-ALWGPDPAAA, demonstrating the potential for a pathogen-derived antigen to initiate a response to the self-derived sequence.	RESULTS
138	151	A2-ALWGPDPAAA	chemical	Third, the 1E6 TCR bound to A2-RQFGPDWIVA peptide, within the C. asparagiforme proteome, with approximately 4-fold stronger affinity than A2-ALWGPDPAAA, demonstrating the potential for a pathogen-derived antigen to initiate a response to the self-derived sequence.	RESULTS
53	71	binding affinities	evidence	Finally, these data demonstrate the largest range of binding affinities reported for a natural, endogenous human TCR of more than 3 logs of magnitude (A2-MVWGPDPLYV vs. A2-RQFGPDFPTI).	RESULTS
96	106	endogenous	protein_state	Finally, these data demonstrate the largest range of binding affinities reported for a natural, endogenous human TCR of more than 3 logs of magnitude (A2-MVWGPDPLYV vs. A2-RQFGPDFPTI).	RESULTS
107	112	human	species	Finally, these data demonstrate the largest range of binding affinities reported for a natural, endogenous human TCR of more than 3 logs of magnitude (A2-MVWGPDPLYV vs. A2-RQFGPDFPTI).	RESULTS
113	116	TCR	complex_assembly	Finally, these data demonstrate the largest range of binding affinities reported for a natural, endogenous human TCR of more than 3 logs of magnitude (A2-MVWGPDPLYV vs. A2-RQFGPDFPTI).	RESULTS
151	164	A2-MVWGPDPLYV	chemical	Finally, these data demonstrate the largest range of binding affinities reported for a natural, endogenous human TCR of more than 3 logs of magnitude (A2-MVWGPDPLYV vs. A2-RQFGPDFPTI).	RESULTS
169	182	A2-RQFGPDFPTI	chemical	Finally, these data demonstrate the largest range of binding affinities reported for a natural, endogenous human TCR of more than 3 logs of magnitude (A2-MVWGPDPLYV vs. A2-RQFGPDFPTI).	RESULTS
15	23	affinity	evidence	To confirm the affinity spread detected by SPR, and to evaluate whether experiments performed using soluble molecules were biologically relevant to events at the T cell surface, we determined the effective 2D affinity of each APL using an adhesion frequency assay in which a human rbc coated in pMHC acted as an adhesion sensor.	RESULTS
43	46	SPR	experimental_method	To confirm the affinity spread detected by SPR, and to evaluate whether experiments performed using soluble molecules were biologically relevant to events at the T cell surface, we determined the effective 2D affinity of each APL using an adhesion frequency assay in which a human rbc coated in pMHC acted as an adhesion sensor.	RESULTS
206	217	2D affinity	evidence	To confirm the affinity spread detected by SPR, and to evaluate whether experiments performed using soluble molecules were biologically relevant to events at the T cell surface, we determined the effective 2D affinity of each APL using an adhesion frequency assay in which a human rbc coated in pMHC acted as an adhesion sensor.	RESULTS
226	229	APL	chemical	To confirm the affinity spread detected by SPR, and to evaluate whether experiments performed using soluble molecules were biologically relevant to events at the T cell surface, we determined the effective 2D affinity of each APL using an adhesion frequency assay in which a human rbc coated in pMHC acted as an adhesion sensor.	RESULTS
239	263	adhesion frequency assay	experimental_method	To confirm the affinity spread detected by SPR, and to evaluate whether experiments performed using soluble molecules were biologically relevant to events at the T cell surface, we determined the effective 2D affinity of each APL using an adhesion frequency assay in which a human rbc coated in pMHC acted as an adhesion sensor.	RESULTS
275	280	human	species	To confirm the affinity spread detected by SPR, and to evaluate whether experiments performed using soluble molecules were biologically relevant to events at the T cell surface, we determined the effective 2D affinity of each APL using an adhesion frequency assay in which a human rbc coated in pMHC acted as an adhesion sensor.	RESULTS
295	299	pMHC	complex_assembly	To confirm the affinity spread detected by SPR, and to evaluate whether experiments performed using soluble molecules were biologically relevant to events at the T cell surface, we determined the effective 2D affinity of each APL using an adhesion frequency assay in which a human rbc coated in pMHC acted as an adhesion sensor.	RESULTS
18	21	SPR	experimental_method	In agreement with SPR experiments, the range of 2D affinities we detected differed by around 3 logs, with the A2-MVWGPDPLYV generating the weakest 2D affinity (2.6 × 10–5 AcKa μm4) and A2-RQFGPDFPTI the strongest (4.5 × 10–2 AcKa μm4) (Figure 2J).	RESULTS
48	61	2D affinities	evidence	In agreement with SPR experiments, the range of 2D affinities we detected differed by around 3 logs, with the A2-MVWGPDPLYV generating the weakest 2D affinity (2.6 × 10–5 AcKa μm4) and A2-RQFGPDFPTI the strongest (4.5 × 10–2 AcKa μm4) (Figure 2J).	RESULTS
110	123	A2-MVWGPDPLYV	chemical	In agreement with SPR experiments, the range of 2D affinities we detected differed by around 3 logs, with the A2-MVWGPDPLYV generating the weakest 2D affinity (2.6 × 10–5 AcKa μm4) and A2-RQFGPDFPTI the strongest (4.5 × 10–2 AcKa μm4) (Figure 2J).	RESULTS
147	158	2D affinity	evidence	In agreement with SPR experiments, the range of 2D affinities we detected differed by around 3 logs, with the A2-MVWGPDPLYV generating the weakest 2D affinity (2.6 × 10–5 AcKa μm4) and A2-RQFGPDFPTI the strongest (4.5 × 10–2 AcKa μm4) (Figure 2J).	RESULTS
171	175	AcKa	evidence	In agreement with SPR experiments, the range of 2D affinities we detected differed by around 3 logs, with the A2-MVWGPDPLYV generating the weakest 2D affinity (2.6 × 10–5 AcKa μm4) and A2-RQFGPDFPTI the strongest (4.5 × 10–2 AcKa μm4) (Figure 2J).	RESULTS
185	198	A2-RQFGPDFPTI	chemical	In agreement with SPR experiments, the range of 2D affinities we detected differed by around 3 logs, with the A2-MVWGPDPLYV generating the weakest 2D affinity (2.6 × 10–5 AcKa μm4) and A2-RQFGPDFPTI the strongest (4.5 × 10–2 AcKa μm4) (Figure 2J).	RESULTS
225	229	AcKa	evidence	In agreement with SPR experiments, the range of 2D affinities we detected differed by around 3 logs, with the A2-MVWGPDPLYV generating the weakest 2D affinity (2.6 × 10–5 AcKa μm4) and A2-RQFGPDFPTI the strongest (4.5 × 10–2 AcKa μm4) (Figure 2J).	RESULTS
12	23	3D affinity	evidence	As with the 3D affinity measurements, the 2D affinity measurements correlated well with the EC50 values for each ligand (Figure 2K) demonstrating a strong correlation (Pearson’s correlation = 0.8, P = 0.01) between T cell antigen sensitivity and TCR binding affinity.	RESULTS
42	53	2D affinity	evidence	As with the 3D affinity measurements, the 2D affinity measurements correlated well with the EC50 values for each ligand (Figure 2K) demonstrating a strong correlation (Pearson’s correlation = 0.8, P = 0.01) between T cell antigen sensitivity and TCR binding affinity.	RESULTS
92	96	EC50	evidence	As with the 3D affinity measurements, the 2D affinity measurements correlated well with the EC50 values for each ligand (Figure 2K) demonstrating a strong correlation (Pearson’s correlation = 0.8, P = 0.01) between T cell antigen sensitivity and TCR binding affinity.	RESULTS
168	189	Pearson’s correlation	evidence	As with the 3D affinity measurements, the 2D affinity measurements correlated well with the EC50 values for each ligand (Figure 2K) demonstrating a strong correlation (Pearson’s correlation = 0.8, P = 0.01) between T cell antigen sensitivity and TCR binding affinity.	RESULTS
197	198	P	evidence	As with the 3D affinity measurements, the 2D affinity measurements correlated well with the EC50 values for each ligand (Figure 2K) demonstrating a strong correlation (Pearson’s correlation = 0.8, P = 0.01) between T cell antigen sensitivity and TCR binding affinity.	RESULTS
246	266	TCR binding affinity	evidence	As with the 3D affinity measurements, the 2D affinity measurements correlated well with the EC50 values for each ligand (Figure 2K) demonstrating a strong correlation (Pearson’s correlation = 0.8, P = 0.01) between T cell antigen sensitivity and TCR binding affinity.	RESULTS
62	73	3D affinity	evidence	Of note, these data demonstrate a close agreement between the 3D affinity values generated using SPR and 2D affinity values generated using adhesion frequency assays.	RESULTS
97	100	SPR	experimental_method	Of note, these data demonstrate a close agreement between the 3D affinity values generated using SPR and 2D affinity values generated using adhesion frequency assays.	RESULTS
105	116	2D affinity	evidence	Of note, these data demonstrate a close agreement between the 3D affinity values generated using SPR and 2D affinity values generated using adhesion frequency assays.	RESULTS
4	11	1E6 TCR	complex_assembly	The 1E6 TCR uses a consensus binding mode to engage multiple APLs.	RESULTS
61	65	APLs	chemical	The 1E6 TCR uses a consensus binding mode to engage multiple APLs.	RESULTS
13	22	structure	evidence	Our previous structure of the 1E6-A2-ALWGPDPAAA complex demonstrated a limited binding footprint between the TCR and pMHC.	RESULTS
30	47	1E6-A2-ALWGPDPAAA	complex_assembly	Our previous structure of the 1E6-A2-ALWGPDPAAA complex demonstrated a limited binding footprint between the TCR and pMHC.	RESULTS
79	96	binding footprint	site	Our previous structure of the 1E6-A2-ALWGPDPAAA complex demonstrated a limited binding footprint between the TCR and pMHC.	RESULTS
109	112	TCR	complex_assembly	Our previous structure of the 1E6-A2-ALWGPDPAAA complex demonstrated a limited binding footprint between the TCR and pMHC.	RESULTS
117	121	pMHC	complex_assembly	Our previous structure of the 1E6-A2-ALWGPDPAAA complex demonstrated a limited binding footprint between the TCR and pMHC.	RESULTS
87	103	binding affinity	evidence	The low number of contacts between the 2 molecules most likely contributed to the weak binding affinity of the interaction.	RESULTS
47	54	1E6 TCR	complex_assembly	In order to examine the mechanism by which the 1E6 TCR engaged a wide range of peptides with divergent binding affinities, we solved the structure of the 1E6 TCR in complex with all 7 APLs used in Figure 2.	RESULTS
103	121	binding affinities	evidence	In order to examine the mechanism by which the 1E6 TCR engaged a wide range of peptides with divergent binding affinities, we solved the structure of the 1E6 TCR in complex with all 7 APLs used in Figure 2.	RESULTS
126	132	solved	experimental_method	In order to examine the mechanism by which the 1E6 TCR engaged a wide range of peptides with divergent binding affinities, we solved the structure of the 1E6 TCR in complex with all 7 APLs used in Figure 2.	RESULTS
137	146	structure	evidence	In order to examine the mechanism by which the 1E6 TCR engaged a wide range of peptides with divergent binding affinities, we solved the structure of the 1E6 TCR in complex with all 7 APLs used in Figure 2.	RESULTS
154	161	1E6 TCR	complex_assembly	In order to examine the mechanism by which the 1E6 TCR engaged a wide range of peptides with divergent binding affinities, we solved the structure of the 1E6 TCR in complex with all 7 APLs used in Figure 2.	RESULTS
162	177	in complex with	protein_state	In order to examine the mechanism by which the 1E6 TCR engaged a wide range of peptides with divergent binding affinities, we solved the structure of the 1E6 TCR in complex with all 7 APLs used in Figure 2.	RESULTS
184	188	APLs	chemical	In order to examine the mechanism by which the 1E6 TCR engaged a wide range of peptides with divergent binding affinities, we solved the structure of the 1E6 TCR in complex with all 7 APLs used in Figure 2.	RESULTS
4	14	structures	evidence	All structures were solved in space group P1 to 2–3 Å resolution with crystallographic Rwork/Rfree ratios within accepted limits as shown in the theoretically expected distribution (ref. and Supplemental Table 1).	RESULTS
20	26	solved	experimental_method	All structures were solved in space group P1 to 2–3 Å resolution with crystallographic Rwork/Rfree ratios within accepted limits as shown in the theoretically expected distribution (ref. and Supplemental Table 1).	RESULTS
87	105	Rwork/Rfree ratios	evidence	All structures were solved in space group P1 to 2–3 Å resolution with crystallographic Rwork/Rfree ratios within accepted limits as shown in the theoretically expected distribution (ref. and Supplemental Table 1).	RESULTS
4	11	1E6 TCR	complex_assembly	The 1E6 TCR used a very similar overall binding modality to engage all of the APLs, with root mean square deviation ranging between 0.81 and 1.12 Å2 (compared with 1E6-A2-ALWGPDPAAA).	RESULTS
78	82	APLs	chemical	The 1E6 TCR used a very similar overall binding modality to engage all of the APLs, with root mean square deviation ranging between 0.81 and 1.12 Å2 (compared with 1E6-A2-ALWGPDPAAA).	RESULTS
89	115	root mean square deviation	evidence	The 1E6 TCR used a very similar overall binding modality to engage all of the APLs, with root mean square deviation ranging between 0.81 and 1.12 Å2 (compared with 1E6-A2-ALWGPDPAAA).	RESULTS
164	181	1E6-A2-ALWGPDPAAA	complex_assembly	The 1E6 TCR used a very similar overall binding modality to engage all of the APLs, with root mean square deviation ranging between 0.81 and 1.12 Å2 (compared with 1E6-A2-ALWGPDPAAA).	RESULTS
96	116	TCR binding affinity	evidence	The relatively broad range of buried surface areas (1,670–1,920 Å2) did not correlate well with TCR binding affinity (Pearson’s correlation = 0.45, P = 0.2).	RESULTS
118	139	Pearson’s correlation	evidence	The relatively broad range of buried surface areas (1,670–1,920 Å2) did not correlate well with TCR binding affinity (Pearson’s correlation = 0.45, P = 0.2).	RESULTS
148	149	P	evidence	The relatively broad range of buried surface areas (1,670–1,920 Å2) did not correlate well with TCR binding affinity (Pearson’s correlation = 0.45, P = 0.2).	RESULTS
4	34	surface complementarity values	evidence	The surface complementarity values (0.52–0.7) correlated slightly with affinity (Pearson’s correlation = 0.7, P = 0.05) but could not explain all differences in binding (Figure 3A and Table 2).	RESULTS
71	79	affinity	evidence	The surface complementarity values (0.52–0.7) correlated slightly with affinity (Pearson’s correlation = 0.7, P = 0.05) but could not explain all differences in binding (Figure 3A and Table 2).	RESULTS
81	102	Pearson’s correlation	evidence	The surface complementarity values (0.52–0.7) correlated slightly with affinity (Pearson’s correlation = 0.7, P = 0.05) but could not explain all differences in binding (Figure 3A and Table 2).	RESULTS
110	111	P	evidence	The surface complementarity values (0.52–0.7) correlated slightly with affinity (Pearson’s correlation = 0.7, P = 0.05) but could not explain all differences in binding (Figure 3A and Table 2).	RESULTS
4	7	TCR	complex_assembly	The TCR CDR loops were in a very similar position in all complexes, apart from some slight deviations in the TCR β-chain (Figure 3B); the peptides were all presented in a similar conformation (Figure 3C); and there was minimal variation in crossing angles of the TCR (42.3°–45.6°) (Figure 3D).	RESULTS
8	17	CDR loops	structure_element	The TCR CDR loops were in a very similar position in all complexes, apart from some slight deviations in the TCR β-chain (Figure 3B); the peptides were all presented in a similar conformation (Figure 3C); and there was minimal variation in crossing angles of the TCR (42.3°–45.6°) (Figure 3D).	RESULTS
109	112	TCR	complex_assembly	The TCR CDR loops were in a very similar position in all complexes, apart from some slight deviations in the TCR β-chain (Figure 3B); the peptides were all presented in a similar conformation (Figure 3C); and there was minimal variation in crossing angles of the TCR (42.3°–45.6°) (Figure 3D).	RESULTS
113	120	β-chain	structure_element	The TCR CDR loops were in a very similar position in all complexes, apart from some slight deviations in the TCR β-chain (Figure 3B); the peptides were all presented in a similar conformation (Figure 3C); and there was minimal variation in crossing angles of the TCR (42.3°–45.6°) (Figure 3D).	RESULTS
263	266	TCR	complex_assembly	The TCR CDR loops were in a very similar position in all complexes, apart from some slight deviations in the TCR β-chain (Figure 3B); the peptides were all presented in a similar conformation (Figure 3C); and there was minimal variation in crossing angles of the TCR (42.3°–45.6°) (Figure 3D).	RESULTS
13	20	1E6 TCR	complex_assembly	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
66	69	APL	chemical	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
79	82	TCR	complex_assembly	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
83	90	α-chain	structure_element	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
111	122	MHC class I	complex_assembly	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
124	128	MHCI	complex_assembly	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
130	138	α2-helix	structure_element	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
147	150	TCR	complex_assembly	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
151	158	β-chain	structure_element	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
168	172	MHCI	complex_assembly	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
173	182	α-1 helix	structure_element	Overall, the 1E6 TCR used a canonical binding mode to engage each APL with the TCR α-chain positioned over the MHC class I (MHCI) α2-helix and the TCR β-chain over the MHCI α-1 helix, straddling the peptide cargo.	RESULTS
46	56	interfaces	site	However, subtle differences in the respective interfaces were apparent (discussed below) and resulted in altered binding affinities of the respective complexes.	RESULTS
113	131	binding affinities	evidence	However, subtle differences in the respective interfaces were apparent (discussed below) and resulted in altered binding affinities of the respective complexes.	RESULTS
25	32	1E6 TCR	complex_assembly	Interactions between the 1E6 TCR and different APLs are focused around a conserved GPD peptide motif.	RESULTS
47	51	APLs	chemical	Interactions between the 1E6 TCR and different APLs are focused around a conserved GPD peptide motif.	RESULTS
73	82	conserved	protein_state	Interactions between the 1E6 TCR and different APLs are focused around a conserved GPD peptide motif.	RESULTS
83	100	GPD peptide motif	structure_element	Interactions between the 1E6 TCR and different APLs are focused around a conserved GPD peptide motif.	RESULTS
30	45	atomic analysis	experimental_method	We next performed an in-depth atomic analysis of the contacts between the 1E6 TCR and each APL to determine the structural basis for the altered T cell peptide sensitivities and TCR binding affinities (Table 2).	RESULTS
74	81	1E6 TCR	complex_assembly	We next performed an in-depth atomic analysis of the contacts between the 1E6 TCR and each APL to determine the structural basis for the altered T cell peptide sensitivities and TCR binding affinities (Table 2).	RESULTS
91	94	APL	chemical	We next performed an in-depth atomic analysis of the contacts between the 1E6 TCR and each APL to determine the structural basis for the altered T cell peptide sensitivities and TCR binding affinities (Table 2).	RESULTS
178	200	TCR binding affinities	evidence	We next performed an in-depth atomic analysis of the contacts between the 1E6 TCR and each APL to determine the structural basis for the altered T cell peptide sensitivities and TCR binding affinities (Table 2).	RESULTS
40	47	1E6 TCR	complex_assembly	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
63	67	APLs	chemical	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
164	167	TCR	complex_assembly	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
177	183	Tyr97α	residue_name_number	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
188	194	Trp97β	residue_name_number	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
207	219	aromatic cap	structure_element	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
235	244	GPD motif	structure_element	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
276	280	APLs	chemical	Concomitant with our global analysis of 1E6 TCR binding to the APLs, we observed a common interaction element, consistent with our previous findings, that utilized TCR residues Tyr97α and Trp97β, forming an aromatic cap over a central GPD motif that was present in all of the APLs (Figure 4).	RESULTS
29	32	TCR	complex_assembly	Interactions between these 2 TCR and 3 peptide residues accounted for 41%–50% of the total contacts across all complexes (Table 2), demonstrating the conserved peptide centric binding mode utilized by the 1E6 TCR.	RESULTS
150	159	conserved	protein_state	Interactions between these 2 TCR and 3 peptide residues accounted for 41%–50% of the total contacts across all complexes (Table 2), demonstrating the conserved peptide centric binding mode utilized by the 1E6 TCR.	RESULTS
205	212	1E6 TCR	complex_assembly	Interactions between these 2 TCR and 3 peptide residues accounted for 41%–50% of the total contacts across all complexes (Table 2), demonstrating the conserved peptide centric binding mode utilized by the 1E6 TCR.	RESULTS
84	92	TCR-pMHC	complex_assembly	This fixed anchoring between the 2 molecules was important for stabilization of the TCR-pMHC complex, as — although other peptides without the ‘GDP’ motif were tested and shown to activate the 1E6 T cell clone — we were unable to measure robust affinities using SPR (data not shown).	RESULTS
143	154	‘GDP’ motif	structure_element	This fixed anchoring between the 2 molecules was important for stabilization of the TCR-pMHC complex, as — although other peptides without the ‘GDP’ motif were tested and shown to activate the 1E6 T cell clone — we were unable to measure robust affinities using SPR (data not shown).	RESULTS
245	255	affinities	evidence	This fixed anchoring between the 2 molecules was important for stabilization of the TCR-pMHC complex, as — although other peptides without the ‘GDP’ motif were tested and shown to activate the 1E6 T cell clone — we were unable to measure robust affinities using SPR (data not shown).	RESULTS
262	265	SPR	experimental_method	This fixed anchoring between the 2 molecules was important for stabilization of the TCR-pMHC complex, as — although other peptides without the ‘GDP’ motif were tested and shown to activate the 1E6 T cell clone — we were unable to measure robust affinities using SPR (data not shown).	RESULTS
41	50	conserved	protein_state	These data support the requirement for a conserved interaction between the 1E6 TCR and the GPD motif, as we observed in our previously published 1E6-A2-ALWGPDPAAA structure.	RESULTS
75	82	1E6 TCR	complex_assembly	These data support the requirement for a conserved interaction between the 1E6 TCR and the GPD motif, as we observed in our previously published 1E6-A2-ALWGPDPAAA structure.	RESULTS
91	100	GPD motif	structure_element	These data support the requirement for a conserved interaction between the 1E6 TCR and the GPD motif, as we observed in our previously published 1E6-A2-ALWGPDPAAA structure.	RESULTS
145	162	1E6-A2-ALWGPDPAAA	complex_assembly	These data support the requirement for a conserved interaction between the 1E6 TCR and the GPD motif, as we observed in our previously published 1E6-A2-ALWGPDPAAA structure.	RESULTS
163	172	structure	evidence	These data support the requirement for a conserved interaction between the 1E6 TCR and the GPD motif, as we observed in our previously published 1E6-A2-ALWGPDPAAA structure.	RESULTS
33	42	conserved	protein_state	Focused hotspot binding around a conserved GPD motif enables the 1E6 TCR to tolerate peptide degeneracy.	RESULTS
43	52	GPD motif	structure_element	Focused hotspot binding around a conserved GPD motif enables the 1E6 TCR to tolerate peptide degeneracy.	RESULTS
65	72	1E6 TCR	complex_assembly	Focused hotspot binding around a conserved GPD motif enables the 1E6 TCR to tolerate peptide degeneracy.	RESULTS
13	20	1E6 TCR	complex_assembly	Although the 1E6 TCR formed a similar overall interaction with each APL, the stabilization between the TCR and the GPD motif enabled fine differences in the contact network with both the peptide and MHC surface that allowed discrimination between each ligand (Figure 5).	RESULTS
68	71	APL	chemical	Although the 1E6 TCR formed a similar overall interaction with each APL, the stabilization between the TCR and the GPD motif enabled fine differences in the contact network with both the peptide and MHC surface that allowed discrimination between each ligand (Figure 5).	RESULTS
103	106	TCR	complex_assembly	Although the 1E6 TCR formed a similar overall interaction with each APL, the stabilization between the TCR and the GPD motif enabled fine differences in the contact network with both the peptide and MHC surface that allowed discrimination between each ligand (Figure 5).	RESULTS
115	124	GPD motif	structure_element	Although the 1E6 TCR formed a similar overall interaction with each APL, the stabilization between the TCR and the GPD motif enabled fine differences in the contact network with both the peptide and MHC surface that allowed discrimination between each ligand (Figure 5).	RESULTS
157	172	contact network	site	Although the 1E6 TCR formed a similar overall interaction with each APL, the stabilization between the TCR and the GPD motif enabled fine differences in the contact network with both the peptide and MHC surface that allowed discrimination between each ligand (Figure 5).	RESULTS
187	194	peptide	chemical	Although the 1E6 TCR formed a similar overall interaction with each APL, the stabilization between the TCR and the GPD motif enabled fine differences in the contact network with both the peptide and MHC surface that allowed discrimination between each ligand (Figure 5).	RESULTS
199	210	MHC surface	site	Although the 1E6 TCR formed a similar overall interaction with each APL, the stabilization between the TCR and the GPD motif enabled fine differences in the contact network with both the peptide and MHC surface that allowed discrimination between each ligand (Figure 5).	RESULTS
17	24	1E6 TCR	complex_assembly	For example, the 1E6 TCR made only 47 peptide contacts with A2-MVWGPDPLYV (KD = ~600 μM) compared with 63 and 57 contacts with A2-YQFGPDFPIA (KD = 7.4 μM) and A2-RQFGPDFPTI (KD = 0.5 μM), respectively.	RESULTS
60	73	A2-MVWGPDPLYV	chemical	For example, the 1E6 TCR made only 47 peptide contacts with A2-MVWGPDPLYV (KD = ~600 μM) compared with 63 and 57 contacts with A2-YQFGPDFPIA (KD = 7.4 μM) and A2-RQFGPDFPTI (KD = 0.5 μM), respectively.	RESULTS
75	77	KD	evidence	For example, the 1E6 TCR made only 47 peptide contacts with A2-MVWGPDPLYV (KD = ~600 μM) compared with 63 and 57 contacts with A2-YQFGPDFPIA (KD = 7.4 μM) and A2-RQFGPDFPTI (KD = 0.5 μM), respectively.	RESULTS
127	140	A2-YQFGPDFPIA	chemical	For example, the 1E6 TCR made only 47 peptide contacts with A2-MVWGPDPLYV (KD = ~600 μM) compared with 63 and 57 contacts with A2-YQFGPDFPIA (KD = 7.4 μM) and A2-RQFGPDFPTI (KD = 0.5 μM), respectively.	RESULTS
142	144	KD	evidence	For example, the 1E6 TCR made only 47 peptide contacts with A2-MVWGPDPLYV (KD = ~600 μM) compared with 63 and 57 contacts with A2-YQFGPDFPIA (KD = 7.4 μM) and A2-RQFGPDFPTI (KD = 0.5 μM), respectively.	RESULTS
159	172	A2-RQFGPDFPTI	chemical	For example, the 1E6 TCR made only 47 peptide contacts with A2-MVWGPDPLYV (KD = ~600 μM) compared with 63 and 57 contacts with A2-YQFGPDFPIA (KD = 7.4 μM) and A2-RQFGPDFPTI (KD = 0.5 μM), respectively.	RESULTS
174	176	KD	evidence	For example, the 1E6 TCR made only 47 peptide contacts with A2-MVWGPDPLYV (KD = ~600 μM) compared with 63 and 57 contacts with A2-YQFGPDFPIA (KD = 7.4 μM) and A2-RQFGPDFPTI (KD = 0.5 μM), respectively.	RESULTS
64	84	TCR binding affinity	evidence	Although the number of peptide contacts was a good predictor of TCR binding affinity for some of the APLs, for others, the correlation was poor (Pearson’s correlation = 0.045, P = 0.92), possibly because of different resolutions for each complex structure.	RESULTS
101	105	APLs	chemical	Although the number of peptide contacts was a good predictor of TCR binding affinity for some of the APLs, for others, the correlation was poor (Pearson’s correlation = 0.045, P = 0.92), possibly because of different resolutions for each complex structure.	RESULTS
145	166	Pearson’s correlation	evidence	Although the number of peptide contacts was a good predictor of TCR binding affinity for some of the APLs, for others, the correlation was poor (Pearson’s correlation = 0.045, P = 0.92), possibly because of different resolutions for each complex structure.	RESULTS
246	255	structure	evidence	Although the number of peptide contacts was a good predictor of TCR binding affinity for some of the APLs, for others, the correlation was poor (Pearson’s correlation = 0.045, P = 0.92), possibly because of different resolutions for each complex structure.	RESULTS
17	24	1E6 TCR	complex_assembly	For example, the 1E6 TCR made 64 peptide contacts with A2-YLGGPDFPTI (KD = ~400 μM) compared with 43 contacts with A2-RQWGPDPAAV (KD = 7.8 μM).	RESULTS
55	68	A2-YLGGPDFPTI	chemical	For example, the 1E6 TCR made 64 peptide contacts with A2-YLGGPDFPTI (KD = ~400 μM) compared with 43 contacts with A2-RQWGPDPAAV (KD = 7.8 μM).	RESULTS
70	72	KD	evidence	For example, the 1E6 TCR made 64 peptide contacts with A2-YLGGPDFPTI (KD = ~400 μM) compared with 43 contacts with A2-RQWGPDPAAV (KD = 7.8 μM).	RESULTS
115	128	A2-RQWGPDPAAV	chemical	For example, the 1E6 TCR made 64 peptide contacts with A2-YLGGPDFPTI (KD = ~400 μM) compared with 43 contacts with A2-RQWGPDPAAV (KD = 7.8 μM).	RESULTS
130	132	KD	evidence	For example, the 1E6 TCR made 64 peptide contacts with A2-YLGGPDFPTI (KD = ~400 μM) compared with 43 contacts with A2-RQWGPDPAAV (KD = 7.8 μM).	RESULTS
97	98	1	residue_number	The most important peptide modification in terms of generating new contacts was peptide position 1.	RESULTS
53	56	Arg	residue_name	The stronger ligands all encoded larger side chains (Arg or Tyr) at peptide position 1 (Figure 5, E–H), enabling interactions with 1E6 that were not present in the weaker APLs that lacked large side chains in this position (Figure 5, A, C, and D).	RESULTS
60	63	Tyr	residue_name	The stronger ligands all encoded larger side chains (Arg or Tyr) at peptide position 1 (Figure 5, E–H), enabling interactions with 1E6 that were not present in the weaker APLs that lacked large side chains in this position (Figure 5, A, C, and D).	RESULTS
85	86	1	residue_number	The stronger ligands all encoded larger side chains (Arg or Tyr) at peptide position 1 (Figure 5, E–H), enabling interactions with 1E6 that were not present in the weaker APLs that lacked large side chains in this position (Figure 5, A, C, and D).	RESULTS
171	175	APLs	chemical	The stronger ligands all encoded larger side chains (Arg or Tyr) at peptide position 1 (Figure 5, E–H), enabling interactions with 1E6 that were not present in the weaker APLs that lacked large side chains in this position (Figure 5, A, C, and D).	RESULTS
34	41	1E6 TCR	complex_assembly	We have previously shown that the 1E6 TCR uses a rigid lock-and-key mechanism during binding to A2-ALWGPDPAAA.	RESULTS
96	109	A2-ALWGPDPAAA	chemical	We have previously shown that the 1E6 TCR uses a rigid lock-and-key mechanism during binding to A2-ALWGPDPAAA.	RESULTS
33	42	unligated	protein_state	These data demonstrated that the unligated structure of the 1E6 TCR was virtually identical to its ligated counterparts.	RESULTS
43	52	structure	evidence	These data demonstrated that the unligated structure of the 1E6 TCR was virtually identical to its ligated counterparts.	RESULTS
60	67	1E6 TCR	complex_assembly	These data demonstrated that the unligated structure of the 1E6 TCR was virtually identical to its ligated counterparts.	RESULTS
99	106	ligated	protein_state	These data demonstrated that the unligated structure of the 1E6 TCR was virtually identical to its ligated counterparts.	RESULTS
41	45	APLs	chemical	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
132	151	free binding energy	evidence	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
153	155	ΔG	evidence	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
192	198	solved	experimental_method	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
203	212	unligated	protein_state	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
213	223	structures	evidence	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
233	237	APLs	chemical	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
243	256	A2-ALWGPDPAAA	chemical	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
257	266	structure	evidence	In order to determine whether any of the APLs required an induced fit mechanism during binding that could explain the difference in free binding energy (ΔG) between each complex (Table 2), we solved the unligated structures of all 7 APLs (the A2-ALWGPDPAAA structure has been previously published and was used in this comparison, ref.) (Figure 6 and Supplemental Table 2).	RESULTS
4	13	unligated	protein_state	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
14	27	A2-MVWGPDPLYV	chemical	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
29	31	KD	evidence	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
43	52	structure	evidence	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
82	86	Tyr9	residue_name_number	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
119	128	structure	evidence	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
164	167	TCR	complex_assembly	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
177	183	Asp30β	residue_name_number	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
188	194	Asn51β	residue_name_number	The unligated A2-MVWGPDPLYV (KD = ~600 μM) structure revealed that the side chain Tyr9 swung around 8 Å in the complex structure, subsequently making contacts with TCR residues Asp30β and Asn51β (Figure 6A and Figure 5A, respectively).	RESULTS
75	95	TCR binding affinity	evidence	This movement could result in an entropic penalty contributing to the weak TCR binding affinity we observed for this ligand.	RESULTS
84	88	Asp6	residue_name_number	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
110	123	A2-YLGGPDFPTI	chemical	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
125	127	KD	evidence	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
140	153	A2-ALWGPDPAAA	chemical	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
155	157	KD	evidence	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
174	187	A2-RQFGPDWIVA	chemical	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
189	191	KD	evidence	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
203	213	structures	evidence	Additional small movements in the Cα backbone of the peptide around peptide residue Asp6 were apparent in the A2-YLGGPDFPTI (KD = ~400 μM), A2-ALWGPDPAAA (KD = ~208 μM), and A2-RQFGPDWIVA (KD = 44.4 μM) structures (Figure 6, B, C, and E).	RESULTS
4	13	unligated	protein_state	The unligated structures of A2-AQWGPDAAA, A2-RQWGPDPAAV, A2-YQFGPDFPIA, and A2-RQFGPDFPTI were virtually identical when in complex with 1E6 (Figure 6, D and F–H).	RESULTS
14	24	structures	evidence	The unligated structures of A2-AQWGPDAAA, A2-RQWGPDPAAV, A2-YQFGPDFPIA, and A2-RQFGPDFPTI were virtually identical when in complex with 1E6 (Figure 6, D and F–H).	RESULTS
28	40	A2-AQWGPDAAA	chemical	The unligated structures of A2-AQWGPDAAA, A2-RQWGPDPAAV, A2-YQFGPDFPIA, and A2-RQFGPDFPTI were virtually identical when in complex with 1E6 (Figure 6, D and F–H).	RESULTS
42	55	A2-RQWGPDPAAV	chemical	The unligated structures of A2-AQWGPDAAA, A2-RQWGPDPAAV, A2-YQFGPDFPIA, and A2-RQFGPDFPTI were virtually identical when in complex with 1E6 (Figure 6, D and F–H).	RESULTS
57	70	A2-YQFGPDFPIA	chemical	The unligated structures of A2-AQWGPDAAA, A2-RQWGPDPAAV, A2-YQFGPDFPIA, and A2-RQFGPDFPTI were virtually identical when in complex with 1E6 (Figure 6, D and F–H).	RESULTS
76	89	A2-RQFGPDFPTI	chemical	The unligated structures of A2-AQWGPDAAA, A2-RQWGPDPAAV, A2-YQFGPDFPIA, and A2-RQFGPDFPTI were virtually identical when in complex with 1E6 (Figure 6, D and F–H).	RESULTS
120	135	in complex with	protein_state	The unligated structures of A2-AQWGPDAAA, A2-RQWGPDPAAV, A2-YQFGPDFPIA, and A2-RQFGPDFPTI were virtually identical when in complex with 1E6 (Figure 6, D and F–H).	RESULTS
23	35	A2-AQWGPDAAA	chemical	Apart from the case of A2-AQWGPDAAA (KD = 61.9 μM), these observations support the conclusion that the higher-affinity ligands required less conformational melding during binding, which could be energetically beneficial (lower entopic cost) during ligation with the 1E6 TCR.	RESULTS
37	39	KD	evidence	Apart from the case of A2-AQWGPDAAA (KD = 61.9 μM), these observations support the conclusion that the higher-affinity ligands required less conformational melding during binding, which could be energetically beneficial (lower entopic cost) during ligation with the 1E6 TCR.	RESULTS
110	118	affinity	evidence	Apart from the case of A2-AQWGPDAAA (KD = 61.9 μM), these observations support the conclusion that the higher-affinity ligands required less conformational melding during binding, which could be energetically beneficial (lower entopic cost) during ligation with the 1E6 TCR.	RESULTS
266	273	1E6 TCR	complex_assembly	Apart from the case of A2-AQWGPDAAA (KD = 61.9 μM), these observations support the conclusion that the higher-affinity ligands required less conformational melding during binding, which could be energetically beneficial (lower entopic cost) during ligation with the 1E6 TCR.	RESULTS
56	63	1E6 TCR	complex_assembly	Peptide modifications alter the interaction between the 1E6 TCR and the MHC surface.	RESULTS
72	83	MHC surface	site	Peptide modifications alter the interaction between the 1E6 TCR and the MHC surface.	RESULTS
35	38	TCR	complex_assembly	In addition to changes between the TCR and peptide component, we also observed that different APLs had different knock-on effects between the TCR and MHC.	RESULTS
94	98	APLs	chemical	In addition to changes between the TCR and peptide component, we also observed that different APLs had different knock-on effects between the TCR and MHC.	RESULTS
142	145	TCR	complex_assembly	In addition to changes between the TCR and peptide component, we also observed that different APLs had different knock-on effects between the TCR and MHC.	RESULTS
150	153	MHC	complex_assembly	In addition to changes between the TCR and peptide component, we also observed that different APLs had different knock-on effects between the TCR and MHC.	RESULTS
0	3	MHC	complex_assembly	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
12	17	Arg65	residue_name_number	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
41	62	MHC restriction triad	site	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
64	69	Arg65	residue_name_number	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
71	76	Ala69	residue_name_number	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
82	88	Gln155	residue_name_number	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
115	118	TCR	complex_assembly	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
119	122	MHC	complex_assembly	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
138	144	Gln155	residue_name_number	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
179	184	Ala69	residue_name_number	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
219	228	interface	site	MHC residue Arg65 that forms part of the MHC restriction triad (Arg65, Ala69, and Gln155) played a central role in TCR-MHC contacts, with Gln155 playing a less important role and Ala69 playing no role in binding at the interface (Figure 7).	RESULTS
22	30	affinity	evidence	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
31	35	APLs	chemical	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
65	68	MHC	complex_assembly	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
125	133	affinity	evidence	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
134	138	APLs	chemical	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
182	209	Pearson’s correlation value	evidence	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
231	234	TCR	complex_assembly	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
263	271	affinity	evidence	Generally, the weaker-affinity APLs made fewer contacts with the MHC surface (27–29 interactions) compared with the stronger-affinity APLs (29–35 contacts), consistent with a better Pearson’s correlation value (0.55) compared with TCR-peptide interactions versus affinity (0.045).	RESULTS
41	44	TCR	complex_assembly	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
53	59	Val53β	residue_name_number	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
64	67	MHC	complex_assembly	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
76	81	Gln72	residue_name_number	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
89	93	APLs	chemical	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
120	128	affinity	evidence	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
142	159	1E6-A2-MVWGPDPLYV	complex_assembly	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
189	192	TCR	complex_assembly	For instance, contacts were made between TCR residue Val53β and MHC residue Gln72 in all APLs except for in the weakest affinity ligand pair, 1E6-A2-MVWGPDPLYV, in which a subtle change in TCR conformation — probably mediated by different peptide contacts — abrogated this interaction (Figure 7A).	RESULTS
50	57	entropy	evidence	An energetic switch from unfavorable to favorable entropy (order-to-disorder) correlates with antigen potency.	RESULTS
20	35	contact network	site	Our analysis of the contact network provided some clues that could explain the different antigen potencies and binding affinities between the 1E6 TCR and the different APLs.	RESULTS
111	129	binding affinities	evidence	Our analysis of the contact network provided some clues that could explain the different antigen potencies and binding affinities between the 1E6 TCR and the different APLs.	RESULTS
142	149	1E6 TCR	complex_assembly	Our analysis of the contact network provided some clues that could explain the different antigen potencies and binding affinities between the 1E6 TCR and the different APLs.	RESULTS
168	172	APLs	chemical	Our analysis of the contact network provided some clues that could explain the different antigen potencies and binding affinities between the 1E6 TCR and the different APLs.	RESULTS
17	24	1E6 TCR	complex_assembly	For example, the 1E6 TCR bound to A2-RQWGPDPAAV with the third strongest affinity (KD = 7.8 μM) but made fewer contacts than with A2-ALWGPDPAAA (KD = ~208 μM) (Table 2).	RESULTS
25	33	bound to	protein_state	For example, the 1E6 TCR bound to A2-RQWGPDPAAV with the third strongest affinity (KD = 7.8 μM) but made fewer contacts than with A2-ALWGPDPAAA (KD = ~208 μM) (Table 2).	RESULTS
34	47	A2-RQWGPDPAAV	chemical	For example, the 1E6 TCR bound to A2-RQWGPDPAAV with the third strongest affinity (KD = 7.8 μM) but made fewer contacts than with A2-ALWGPDPAAA (KD = ~208 μM) (Table 2).	RESULTS
73	81	affinity	evidence	For example, the 1E6 TCR bound to A2-RQWGPDPAAV with the third strongest affinity (KD = 7.8 μM) but made fewer contacts than with A2-ALWGPDPAAA (KD = ~208 μM) (Table 2).	RESULTS
83	85	KD	evidence	For example, the 1E6 TCR bound to A2-RQWGPDPAAV with the third strongest affinity (KD = 7.8 μM) but made fewer contacts than with A2-ALWGPDPAAA (KD = ~208 μM) (Table 2).	RESULTS
130	143	A2-ALWGPDPAAA	chemical	For example, the 1E6 TCR bound to A2-RQWGPDPAAV with the third strongest affinity (KD = 7.8 μM) but made fewer contacts than with A2-ALWGPDPAAA (KD = ~208 μM) (Table 2).	RESULTS
145	147	KD	evidence	For example, the 1E6 TCR bound to A2-RQWGPDPAAV with the third strongest affinity (KD = 7.8 μM) but made fewer contacts than with A2-ALWGPDPAAA (KD = ~208 μM) (Table 2).	RESULTS
31	53	thermodynamic analysis	experimental_method	Thus, we performed an in-depth thermodynamic analysis of 6 of the ligands under investigation (Figure 8 and Supplemental Table 3).	RESULTS
9	25	binding affinity	evidence	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
42	55	A2-MVWGPDPLYV	chemical	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
60	73	A2-YLGGPDFPTI	chemical	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
156	165	enthalpic	evidence	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
167	170	ΔH°	evidence	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
176	184	entropic	evidence	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
186	190	TΔS°	evidence	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
234	252	binding affinities	evidence	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
272	275	APL	chemical	The weak binding affinity between 1E6 and A2-MVWGPDPLYV and A2-YLGGPDFPTI generated thermodynamic data that were not robust enough to gain insight into the enthalpic (ΔH°) and entropic (TΔS°) changes that contributed to the different binding affinities/potencies for each APL.	RESULTS
12	33	free binding energies	evidence	The overall free binding energies (ΔG°) were between –4.4 and –8.6 kcal/mol, reflecting the wide range of TCR binding affinities we observed for the different APLs.	RESULTS
35	38	ΔG°	evidence	The overall free binding energies (ΔG°) were between –4.4 and –8.6 kcal/mol, reflecting the wide range of TCR binding affinities we observed for the different APLs.	RESULTS
106	128	TCR binding affinities	evidence	The overall free binding energies (ΔG°) were between –4.4 and –8.6 kcal/mol, reflecting the wide range of TCR binding affinities we observed for the different APLs.	RESULTS
159	163	APLs	chemical	The overall free binding energies (ΔG°) were between –4.4 and –8.6 kcal/mol, reflecting the wide range of TCR binding affinities we observed for the different APLs.	RESULTS
77	85	affinity	evidence	The enthalpic contribution in each complex did not follow a clear trend with affinity, with all but the 1E6-A2-RQFGPDFPTI interaction (ΔH° = 6.3 kcal/mol) generating an energetically favorable enthalpy value (ΔH° = –3.7 to –11.4 kcal/mol); this indicated a net gain in electrostatic interactions during complex formation.	RESULTS
104	121	1E6-A2-RQFGPDFPTI	complex_assembly	The enthalpic contribution in each complex did not follow a clear trend with affinity, with all but the 1E6-A2-RQFGPDFPTI interaction (ΔH° = 6.3 kcal/mol) generating an energetically favorable enthalpy value (ΔH° = –3.7 to –11.4 kcal/mol); this indicated a net gain in electrostatic interactions during complex formation.	RESULTS
135	138	ΔH°	evidence	The enthalpic contribution in each complex did not follow a clear trend with affinity, with all but the 1E6-A2-RQFGPDFPTI interaction (ΔH° = 6.3 kcal/mol) generating an energetically favorable enthalpy value (ΔH° = –3.7 to –11.4 kcal/mol); this indicated a net gain in electrostatic interactions during complex formation.	RESULTS
193	201	enthalpy	evidence	The enthalpic contribution in each complex did not follow a clear trend with affinity, with all but the 1E6-A2-RQFGPDFPTI interaction (ΔH° = 6.3 kcal/mol) generating an energetically favorable enthalpy value (ΔH° = –3.7 to –11.4 kcal/mol); this indicated a net gain in electrostatic interactions during complex formation.	RESULTS
209	212	ΔH°	evidence	The enthalpic contribution in each complex did not follow a clear trend with affinity, with all but the 1E6-A2-RQFGPDFPTI interaction (ΔH° = 6.3 kcal/mol) generating an energetically favorable enthalpy value (ΔH° = –3.7 to –11.4 kcal/mol); this indicated a net gain in electrostatic interactions during complex formation.	RESULTS
37	44	entropy	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
64	72	affinity	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
86	94	affinity	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
126	153	Pearson’s correlation value	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
162	169	entropy	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
174	182	affinity	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
184	211	Pearson’s correlation value	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
218	219	P	evidence	However, there was a clear switch in entropy between the weaker-affinity and stronger-affinity ligands, indicated by a strong Pearson’s correlation value between entropy and affinity (Pearson’s correlation value 0.93, P =0.007).	RESULTS
18	31	A2-ALWGPDPAAA	chemical	For instance, the A2-ALWGPDPAAA, A2-AQWGPDAAA, and A2-RQFGPDWIVA (KD = ~208 μM, KD = 61.9 μM, and KD = 44.4 μM, respectively) were all entropically unfavorable (TΔS° = –2.9 to –5.6 kcal/mol), indicating a net change from disorder to order.	RESULTS
33	45	A2-AQWGPDAAA	chemical	For instance, the A2-ALWGPDPAAA, A2-AQWGPDAAA, and A2-RQFGPDWIVA (KD = ~208 μM, KD = 61.9 μM, and KD = 44.4 μM, respectively) were all entropically unfavorable (TΔS° = –2.9 to –5.6 kcal/mol), indicating a net change from disorder to order.	RESULTS
51	64	A2-RQFGPDWIVA	chemical	For instance, the A2-ALWGPDPAAA, A2-AQWGPDAAA, and A2-RQFGPDWIVA (KD = ~208 μM, KD = 61.9 μM, and KD = 44.4 μM, respectively) were all entropically unfavorable (TΔS° = –2.9 to –5.6 kcal/mol), indicating a net change from disorder to order.	RESULTS
66	68	KD	evidence	For instance, the A2-ALWGPDPAAA, A2-AQWGPDAAA, and A2-RQFGPDWIVA (KD = ~208 μM, KD = 61.9 μM, and KD = 44.4 μM, respectively) were all entropically unfavorable (TΔS° = –2.9 to –5.6 kcal/mol), indicating a net change from disorder to order.	RESULTS
80	82	KD	evidence	For instance, the A2-ALWGPDPAAA, A2-AQWGPDAAA, and A2-RQFGPDWIVA (KD = ~208 μM, KD = 61.9 μM, and KD = 44.4 μM, respectively) were all entropically unfavorable (TΔS° = –2.9 to –5.6 kcal/mol), indicating a net change from disorder to order.	RESULTS
98	100	KD	evidence	For instance, the A2-ALWGPDPAAA, A2-AQWGPDAAA, and A2-RQFGPDWIVA (KD = ~208 μM, KD = 61.9 μM, and KD = 44.4 μM, respectively) were all entropically unfavorable (TΔS° = –2.9 to –5.6 kcal/mol), indicating a net change from disorder to order.	RESULTS
161	165	TΔS°	evidence	For instance, the A2-ALWGPDPAAA, A2-AQWGPDAAA, and A2-RQFGPDWIVA (KD = ~208 μM, KD = 61.9 μM, and KD = 44.4 μM, respectively) were all entropically unfavorable (TΔS° = –2.9 to –5.6 kcal/mol), indicating a net change from disorder to order.	RESULTS
25	33	affinity	evidence	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
42	55	A2-RQWGPDPAAV	chemical	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
57	59	KD	evidence	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
71	84	A2-YQFGPDFPIA	chemical	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
86	88	KD	evidence	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
104	117	A2-RQFGPDFPTI	chemical	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
119	121	KD	evidence	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
152	159	entropy	evidence	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
161	165	TΔS°	evidence	Conversely, the stronger-affinity ligands A2-RQWGPDPAAV (KD = 7.8 μM), A2-YQFGPDFPIA (KD = 7.4 μM), and A2-RQFGPDFPTI (KD = 0.5 μM) exhibited favorable entropy (TΔS° = 2.2 to 14.9 kcal/mol), indicating an order-to-disorder change during binding, possibly through the expulsion of ordered water molecules.	RESULTS
35	44	unligated	protein_state	Furthermore, the structures of the unligated pMHCs demonstrated that, for these stronger-affinity ligands, there was less conformational difference between the TCR ligated pMHCs compared with the weaker-affinity ligands (Figure 6).	RESULTS
45	50	pMHCs	complex_assembly	Furthermore, the structures of the unligated pMHCs demonstrated that, for these stronger-affinity ligands, there was less conformational difference between the TCR ligated pMHCs compared with the weaker-affinity ligands (Figure 6).	RESULTS
89	97	affinity	evidence	Furthermore, the structures of the unligated pMHCs demonstrated that, for these stronger-affinity ligands, there was less conformational difference between the TCR ligated pMHCs compared with the weaker-affinity ligands (Figure 6).	RESULTS
160	163	TCR	complex_assembly	Furthermore, the structures of the unligated pMHCs demonstrated that, for these stronger-affinity ligands, there was less conformational difference between the TCR ligated pMHCs compared with the weaker-affinity ligands (Figure 6).	RESULTS
164	171	ligated	protein_state	Furthermore, the structures of the unligated pMHCs demonstrated that, for these stronger-affinity ligands, there was less conformational difference between the TCR ligated pMHCs compared with the weaker-affinity ligands (Figure 6).	RESULTS
172	177	pMHCs	complex_assembly	Furthermore, the structures of the unligated pMHCs demonstrated that, for these stronger-affinity ligands, there was less conformational difference between the TCR ligated pMHCs compared with the weaker-affinity ligands (Figure 6).	RESULTS
203	211	affinity	evidence	Furthermore, the structures of the unligated pMHCs demonstrated that, for these stronger-affinity ligands, there was less conformational difference between the TCR ligated pMHCs compared with the weaker-affinity ligands (Figure 6).	RESULTS
92	100	affinity	evidence	The potential requirement for a larger degree of induced fit during binding to these weaker-affinity ligands is consistent with the larger entropic penalties observed for these interactions.	RESULTS
23	30	1E6 TCR	complex_assembly	Potential epitopes for 1E6 TCR occur commonly in the viral proteome.	RESULTS
53	58	viral	taxonomy_domain	Potential epitopes for 1E6 TCR occur commonly in the viral proteome.	RESULTS
56	64	peptides	chemical	We searched a database of over 1,924,572 unique decamer peptides from the proteome of viral pathogens that are known, or strongly suspected, to infect humans.	RESULTS
86	91	viral	taxonomy_domain	We searched a database of over 1,924,572 unique decamer peptides from the proteome of viral pathogens that are known, or strongly suspected, to infect humans.	RESULTS
151	157	humans	species	We searched a database of over 1,924,572 unique decamer peptides from the proteome of viral pathogens that are known, or strongly suspected, to infect humans.	RESULTS
65	75	xxxGPDxxxx	structure_element	Three hundred forty-two of these decamers conformed to the motif xxxGPDxxxx.	RESULTS
42	52	xOxGPDxxxO	structure_element	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
108	109	A	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
110	111	V	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
113	114	I	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
116	117	L	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
119	120	M	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
122	123	Y	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
125	126	F	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
132	133	W	residue_name	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
162	172	HLA-A*0201	protein	Of these, 53 peptides contained the motif xOxGPDxxxO, where O is one of the hydrophobic amino acid residues A,V, I, L, M, Y, F, and W that might allow binding to HLA-A*0201 (Supplemental Table 4).	RESULTS
104	114	MVWGPDPLYV	chemical	Thus, there are many pathogen-encoded peptides that could act as agonists for the 1E6 T cell beyond the MVWGPDPLYV and RQFGPDWIVA sequences studied here.	RESULTS
119	129	RQFGPDWIVA	chemical	Thus, there are many pathogen-encoded peptides that could act as agonists for the 1E6 T cell beyond the MVWGPDPLYV and RQFGPDWIVA sequences studied here.	RESULTS
61	70	bacterial	taxonomy_domain	Extension of these analyses to include the larger genomes of bacterial pathogens would be expected to considerably increase these numbers.	RESULTS
4	20	binding affinity	evidence	The binding affinity of the 1E6 TCR interaction with A2-RQFGPDWIVA is considerably higher than with the disease-implicated A2-ALWGPDPAAA sequence (KD = 44.4 μM and KD > 200 μM, respectively), highlighting how a pathogen-derived sequence might be capable of priming a 1E6-like T cell.	RESULTS
28	35	1E6 TCR	complex_assembly	The binding affinity of the 1E6 TCR interaction with A2-RQFGPDWIVA is considerably higher than with the disease-implicated A2-ALWGPDPAAA sequence (KD = 44.4 μM and KD > 200 μM, respectively), highlighting how a pathogen-derived sequence might be capable of priming a 1E6-like T cell.	RESULTS
53	66	A2-RQFGPDWIVA	chemical	The binding affinity of the 1E6 TCR interaction with A2-RQFGPDWIVA is considerably higher than with the disease-implicated A2-ALWGPDPAAA sequence (KD = 44.4 μM and KD > 200 μM, respectively), highlighting how a pathogen-derived sequence might be capable of priming a 1E6-like T cell.	RESULTS
123	136	A2-ALWGPDPAAA	chemical	The binding affinity of the 1E6 TCR interaction with A2-RQFGPDWIVA is considerably higher than with the disease-implicated A2-ALWGPDPAAA sequence (KD = 44.4 μM and KD > 200 μM, respectively), highlighting how a pathogen-derived sequence might be capable of priming a 1E6-like T cell.	RESULTS
147	149	KD	evidence	The binding affinity of the 1E6 TCR interaction with A2-RQFGPDWIVA is considerably higher than with the disease-implicated A2-ALWGPDPAAA sequence (KD = 44.4 μM and KD > 200 μM, respectively), highlighting how a pathogen-derived sequence might be capable of priming a 1E6-like T cell.	RESULTS
164	166	KD	evidence	The binding affinity of the 1E6 TCR interaction with A2-RQFGPDWIVA is considerably higher than with the disease-implicated A2-ALWGPDPAAA sequence (KD = 44.4 μM and KD > 200 μM, respectively), highlighting how a pathogen-derived sequence might be capable of priming a 1E6-like T cell.	RESULTS
91	94	TCR	complex_assembly	T cell antigen discrimination is governed by an interaction between the clonally expressed TCR and pMHC, mediated by the chemical characteristics of the interacting molecules.	DISCUSS
99	103	pMHC	complex_assembly	T cell antigen discrimination is governed by an interaction between the clonally expressed TCR and pMHC, mediated by the chemical characteristics of the interacting molecules.	DISCUSS
34	37	TCR	complex_assembly	It has recently become clear that TCR cross-reactivity with large numbers of different pMHC ligands is essential to plug holes in T cell immune coverage that pathogens could exploit.	DISCUSS
87	91	pMHC	complex_assembly	It has recently become clear that TCR cross-reactivity with large numbers of different pMHC ligands is essential to plug holes in T cell immune coverage that pathogens could exploit.	DISCUSS
19	28	interface	site	Flexibility at the interface between the TCR and pMHC, demonstrated in various studies, has been suggested as a mechanism mediating T cell cross-reactivity with multiple distinct epitopes.	DISCUSS
41	44	TCR	complex_assembly	Flexibility at the interface between the TCR and pMHC, demonstrated in various studies, has been suggested as a mechanism mediating T cell cross-reactivity with multiple distinct epitopes.	DISCUSS
49	53	pMHC	complex_assembly	Flexibility at the interface between the TCR and pMHC, demonstrated in various studies, has been suggested as a mechanism mediating T cell cross-reactivity with multiple distinct epitopes.	DISCUSS
38	47	CDR loops	structure_element	This notion is attractive because the CDR loops, which form the TCR antigen-binding site, are usually the most flexible part of the TCR and have the ability to mold around differently shaped ligands.	DISCUSS
64	88	TCR antigen-binding site	site	This notion is attractive because the CDR loops, which form the TCR antigen-binding site, are usually the most flexible part of the TCR and have the ability to mold around differently shaped ligands.	DISCUSS
132	135	TCR	complex_assembly	This notion is attractive because the CDR loops, which form the TCR antigen-binding site, are usually the most flexible part of the TCR and have the ability to mold around differently shaped ligands.	DISCUSS
109	112	TCR	complex_assembly	Focused binding around a minimal peptide motif has also been implicated as an alternative mechanism enabling TCR cross-reactivity.	DISCUSS
69	81	alloreactive	protein_state	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
82	88	murine	taxonomy_domain	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
89	92	TCR	complex_assembly	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
93	96	MHC	complex_assembly	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
109	113	42F3	protein	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
114	117	TCR	complex_assembly	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
122	127	H2-Ld	protein	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
199	208	conserved	protein_state	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
209	216	hotspot	site	Notably among these studies, Garcia and colleagues recently used the alloreactive murine TCR-MHC pair of the 42F3 TCR and H2-Ld to demonstrate recognition of a large number of different peptides via conserved hotspot contacts with prominent up-facing peptide residues.	DISCUSS
52	57	MHCII	protein_type	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
69	76	Hy.1B11	protein	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
77	80	TCR	complex_assembly	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
161	172	deep pocket	site	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
202	203	2	residue_number	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
205	206	3	residue_number	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
212	213	5	residue_number	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
220	228	MBP85–99	protein	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
229	237	bound to	protein_state	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
238	245	HLA-DQ1	protein	Sethi and colleagues recently demonstrated that the MHCII-restricted Hy.1B11 TCR, which was isolated from a patient with multiple sclerosis, could anchor into a deep pocket formed from peptide residues 2, 3, and 5 (from MBP85–99 bound to HLA-DQ1).	DISCUSS
15	24	conserved	protein_state	This motif was conserved in at least 2 potential foreign peptides, originating from Herpes simplex virus and Pseudomonas aeruginosa, enabling TCR recognition of foreign epitopes.	DISCUSS
84	104	Herpes simplex virus	species	This motif was conserved in at least 2 potential foreign peptides, originating from Herpes simplex virus and Pseudomonas aeruginosa, enabling TCR recognition of foreign epitopes.	DISCUSS
109	131	Pseudomonas aeruginosa	species	This motif was conserved in at least 2 potential foreign peptides, originating from Herpes simplex virus and Pseudomonas aeruginosa, enabling TCR recognition of foreign epitopes.	DISCUSS
142	145	TCR	complex_assembly	This motif was conserved in at least 2 potential foreign peptides, originating from Herpes simplex virus and Pseudomonas aeruginosa, enabling TCR recognition of foreign epitopes.	DISCUSS
43	48	human	species	First, we currently know nothing about how human MHCI–restricted TCRs mediate cross-reactivity in the context of a clinically relevant model of autoimmunity, thought to be a major pathway of disease initiation in several autoimmune diseases.	DISCUSS
49	53	MHCI	complex_assembly	First, we currently know nothing about how human MHCI–restricted TCRs mediate cross-reactivity in the context of a clinically relevant model of autoimmunity, thought to be a major pathway of disease initiation in several autoimmune diseases.	DISCUSS
65	69	TCRs	complex_assembly	First, we currently know nothing about how human MHCI–restricted TCRs mediate cross-reactivity in the context of a clinically relevant model of autoimmunity, thought to be a major pathway of disease initiation in several autoimmune diseases.	DISCUSS
84	87	TCR	complex_assembly	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
140	144	allo	protein_state	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
145	152	TCR-MHC	complex_assembly	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
165	169	42F3	protein	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
170	173	TCR	complex_assembly	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
178	183	H2-Ld	protein	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
274	284	structures	evidence	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
290	293	TCR	complex_assembly	Second, molecular studies have not yet revealed a broad set of rules that determine TCR cross-reactivity because, with the exception of the allo–TCR-MHC pair of the 42F3 TCR and H2-Ld that did not encounter each other during T cell development, studies have been limited to structures of a TCR with only 2 or 3 different ligands.	DISCUSS
46	50	MHCI	complex_assembly	Here, we investigated a highly cross-reactive MHCI-restricted TCR isolated from a patient with T1D that recognizes an HLA-A*0201–restricted preproinsulin signal peptide (ALWGPDPAAA15–24).	DISCUSS
62	65	TCR	complex_assembly	Here, we investigated a highly cross-reactive MHCI-restricted TCR isolated from a patient with T1D that recognizes an HLA-A*0201–restricted preproinsulin signal peptide (ALWGPDPAAA15–24).	DISCUSS
118	128	HLA-A*0201	protein	Here, we investigated a highly cross-reactive MHCI-restricted TCR isolated from a patient with T1D that recognizes an HLA-A*0201–restricted preproinsulin signal peptide (ALWGPDPAAA15–24).	DISCUSS
140	153	preproinsulin	protein	Here, we investigated a highly cross-reactive MHCI-restricted TCR isolated from a patient with T1D that recognizes an HLA-A*0201–restricted preproinsulin signal peptide (ALWGPDPAAA15–24).	DISCUSS
154	168	signal peptide	structure_element	Here, we investigated a highly cross-reactive MHCI-restricted TCR isolated from a patient with T1D that recognizes an HLA-A*0201–restricted preproinsulin signal peptide (ALWGPDPAAA15–24).	DISCUSS
170	185	ALWGPDPAAA15–24	chemical	Here, we investigated a highly cross-reactive MHCI-restricted TCR isolated from a patient with T1D that recognizes an HLA-A*0201–restricted preproinsulin signal peptide (ALWGPDPAAA15–24).	DISCUSS
0	5	Human	species	Human CD8+ T cell clones expressing TCRs with this specificity mediate the destruction of β cells, have been found in islets early in infection, and are proposed to be a major driver of disease.	DISCUSS
36	40	TCRs	complex_assembly	Human CD8+ T cell clones expressing TCRs with this specificity mediate the destruction of β cells, have been found in islets early in infection, and are proposed to be a major driver of disease.	DISCUSS
3	9	solved	experimental_method	We solved the structure of the 1E6 TCR with 7 APLs to enable a comprehensive analysis of the molecular basis of TCR degeneracy.	DISCUSS
14	23	structure	evidence	We solved the structure of the 1E6 TCR with 7 APLs to enable a comprehensive analysis of the molecular basis of TCR degeneracy.	DISCUSS
31	38	1E6 TCR	complex_assembly	We solved the structure of the 1E6 TCR with 7 APLs to enable a comprehensive analysis of the molecular basis of TCR degeneracy.	DISCUSS
46	50	APLs	chemical	We solved the structure of the 1E6 TCR with 7 APLs to enable a comprehensive analysis of the molecular basis of TCR degeneracy.	DISCUSS
112	115	TCR	complex_assembly	We solved the structure of the 1E6 TCR with 7 APLs to enable a comprehensive analysis of the molecular basis of TCR degeneracy.	DISCUSS
68	82	binding energy	evidence	Overall, the difference in antigen potency correlated well with the binding energy (ΔG° kcal/mol) of the 1E6 TCR for the different epitopes, which ranged from values of ΔG° = ~–4.4 to –8.6 kcal/mol (calculated from 3D affinity data) or 2D affinity values of AcKa = 2.5 × 10–5 to 4.4 × 10–2 μm4.	DISCUSS
84	87	ΔG°	evidence	Overall, the difference in antigen potency correlated well with the binding energy (ΔG° kcal/mol) of the 1E6 TCR for the different epitopes, which ranged from values of ΔG° = ~–4.4 to –8.6 kcal/mol (calculated from 3D affinity data) or 2D affinity values of AcKa = 2.5 × 10–5 to 4.4 × 10–2 μm4.	DISCUSS
105	112	1E6 TCR	complex_assembly	Overall, the difference in antigen potency correlated well with the binding energy (ΔG° kcal/mol) of the 1E6 TCR for the different epitopes, which ranged from values of ΔG° = ~–4.4 to –8.6 kcal/mol (calculated from 3D affinity data) or 2D affinity values of AcKa = 2.5 × 10–5 to 4.4 × 10–2 μm4.	DISCUSS
169	172	ΔG°	evidence	Overall, the difference in antigen potency correlated well with the binding energy (ΔG° kcal/mol) of the 1E6 TCR for the different epitopes, which ranged from values of ΔG° = ~–4.4 to –8.6 kcal/mol (calculated from 3D affinity data) or 2D affinity values of AcKa = 2.5 × 10–5 to 4.4 × 10–2 μm4.	DISCUSS
215	226	3D affinity	evidence	Overall, the difference in antigen potency correlated well with the binding energy (ΔG° kcal/mol) of the 1E6 TCR for the different epitopes, which ranged from values of ΔG° = ~–4.4 to –8.6 kcal/mol (calculated from 3D affinity data) or 2D affinity values of AcKa = 2.5 × 10–5 to 4.4 × 10–2 μm4.	DISCUSS
236	247	2D affinity	evidence	Overall, the difference in antigen potency correlated well with the binding energy (ΔG° kcal/mol) of the 1E6 TCR for the different epitopes, which ranged from values of ΔG° = ~–4.4 to –8.6 kcal/mol (calculated from 3D affinity data) or 2D affinity values of AcKa = 2.5 × 10–5 to 4.4 × 10–2 μm4.	DISCUSS
258	262	AcKa	evidence	Overall, the difference in antigen potency correlated well with the binding energy (ΔG° kcal/mol) of the 1E6 TCR for the different epitopes, which ranged from values of ΔG° = ~–4.4 to –8.6 kcal/mol (calculated from 3D affinity data) or 2D affinity values of AcKa = 2.5 × 10–5 to 4.4 × 10–2 μm4.	DISCUSS
126	149	TCR 3D binding affinity	evidence	The weaker end of this spectrum extends our understanding of the limits in which T cells can functionally operate in terms of TCR 3D binding affinity and is in line with the types of very low affinity, yet fully functional self-reactive CD8+ T cells we have observed in tumor-infiltrating lymphocytes.	DISCUSS
192	200	affinity	evidence	The weaker end of this spectrum extends our understanding of the limits in which T cells can functionally operate in terms of TCR 3D binding affinity and is in line with the types of very low affinity, yet fully functional self-reactive CD8+ T cells we have observed in tumor-infiltrating lymphocytes.	DISCUSS
33	37	TCRs	complex_assembly	Previous studies of autoreactive TCRs have shown that their binding mode is generally atypical, either due to an unusual binding manner, weak TCR binding affinity, an unstable pMHC, or a combination of these factors.	DISCUSS
142	162	TCR binding affinity	evidence	Previous studies of autoreactive TCRs have shown that their binding mode is generally atypical, either due to an unusual binding manner, weak TCR binding affinity, an unstable pMHC, or a combination of these factors.	DISCUSS
167	175	unstable	protein_state	Previous studies of autoreactive TCRs have shown that their binding mode is generally atypical, either due to an unusual binding manner, weak TCR binding affinity, an unstable pMHC, or a combination of these factors.	DISCUSS
176	180	pMHC	complex_assembly	Previous studies of autoreactive TCRs have shown that their binding mode is generally atypical, either due to an unusual binding manner, weak TCR binding affinity, an unstable pMHC, or a combination of these factors.	DISCUSS
55	58	TCR	complex_assembly	Our data demonstrate the potential for an autoreactive TCR to bind with a conventional binding mode to a stable pMHC with antipathogen-like affinity (KD = 0.5 μM) depending on the peptide sequence.	DISCUSS
105	111	stable	protein_state	Our data demonstrate the potential for an autoreactive TCR to bind with a conventional binding mode to a stable pMHC with antipathogen-like affinity (KD = 0.5 μM) depending on the peptide sequence.	DISCUSS
112	116	pMHC	complex_assembly	Our data demonstrate the potential for an autoreactive TCR to bind with a conventional binding mode to a stable pMHC with antipathogen-like affinity (KD = 0.5 μM) depending on the peptide sequence.	DISCUSS
140	148	affinity	evidence	Our data demonstrate the potential for an autoreactive TCR to bind with a conventional binding mode to a stable pMHC with antipathogen-like affinity (KD = 0.5 μM) depending on the peptide sequence.	DISCUSS
150	152	KD	evidence	Our data demonstrate the potential for an autoreactive TCR to bind with a conventional binding mode to a stable pMHC with antipathogen-like affinity (KD = 0.5 μM) depending on the peptide sequence.	DISCUSS
4	23	structural analysis	experimental_method	Our structural analysis revealed that the 1E6 TCR bound with a conserved conformation across all APLs investigated.	DISCUSS
42	49	1E6 TCR	complex_assembly	Our structural analysis revealed that the 1E6 TCR bound with a conserved conformation across all APLs investigated.	DISCUSS
50	55	bound	protein_state	Our structural analysis revealed that the 1E6 TCR bound with a conserved conformation across all APLs investigated.	DISCUSS
63	85	conserved conformation	protein_state	Our structural analysis revealed that the 1E6 TCR bound with a conserved conformation across all APLs investigated.	DISCUSS
97	101	APLs	chemical	Our structural analysis revealed that the 1E6 TCR bound with a conserved conformation across all APLs investigated.	DISCUSS
73	76	TCR	complex_assembly	This binding orientation was mediated through a focused interaction with TCR residues Tyr97α and Trp97β that formed an aromatic cap over a central ‘GDP’ motif that was common to all APLs.	DISCUSS
86	92	Tyr97α	residue_name_number	This binding orientation was mediated through a focused interaction with TCR residues Tyr97α and Trp97β that formed an aromatic cap over a central ‘GDP’ motif that was common to all APLs.	DISCUSS
97	103	Trp97β	residue_name_number	This binding orientation was mediated through a focused interaction with TCR residues Tyr97α and Trp97β that formed an aromatic cap over a central ‘GDP’ motif that was common to all APLs.	DISCUSS
119	131	aromatic cap	structure_element	This binding orientation was mediated through a focused interaction with TCR residues Tyr97α and Trp97β that formed an aromatic cap over a central ‘GDP’ motif that was common to all APLs.	DISCUSS
147	158	‘GDP’ motif	structure_element	This binding orientation was mediated through a focused interaction with TCR residues Tyr97α and Trp97β that formed an aromatic cap over a central ‘GDP’ motif that was common to all APLs.	DISCUSS
182	186	APLs	chemical	This binding orientation was mediated through a focused interaction with TCR residues Tyr97α and Trp97β that formed an aromatic cap over a central ‘GDP’ motif that was common to all APLs.	DISCUSS
54	63	GPD motif	structure_element	We have previously demonstrated the importance of the GPD motif using a peptide library scan, as well as a CPL scan approach.	DISCUSS
72	92	peptide library scan	experimental_method	We have previously demonstrated the importance of the GPD motif using a peptide library scan, as well as a CPL scan approach.	DISCUSS
107	115	CPL scan	experimental_method	We have previously demonstrated the importance of the GPD motif using a peptide library scan, as well as a CPL scan approach.	DISCUSS
71	77	lacked	protein_state	Although the 1E6 T cell was able to activate weakly with peptides that lacked this motif, we were unable to robustly measure binding affinities or generate complex structures with these ligands, highlighting the central role of this interaction during 1E6 T cell antigen recognition.	DISCUSS
125	143	binding affinities	evidence	Although the 1E6 T cell was able to activate weakly with peptides that lacked this motif, we were unable to robustly measure binding affinities or generate complex structures with these ligands, highlighting the central role of this interaction during 1E6 T cell antigen recognition.	DISCUSS
164	174	structures	evidence	Although the 1E6 T cell was able to activate weakly with peptides that lacked this motif, we were unable to robustly measure binding affinities or generate complex structures with these ligands, highlighting the central role of this interaction during 1E6 T cell antigen recognition.	DISCUSS
178	181	TCR	complex_assembly	This hotspot binding, defined as a localized cluster of interactions that dominate binding energy during protein-protein interactions, has been previously shown to contribute to TCR recognition of MHC as a mechanism that tunes T cell cross-reactivity by providing fixed anchor points that enable TCRs to tolerate a variable peptide cargo.	DISCUSS
197	200	MHC	complex_assembly	This hotspot binding, defined as a localized cluster of interactions that dominate binding energy during protein-protein interactions, has been previously shown to contribute to TCR recognition of MHC as a mechanism that tunes T cell cross-reactivity by providing fixed anchor points that enable TCRs to tolerate a variable peptide cargo.	DISCUSS
296	300	TCRs	complex_assembly	This hotspot binding, defined as a localized cluster of interactions that dominate binding energy during protein-protein interactions, has been previously shown to contribute to TCR recognition of MHC as a mechanism that tunes T cell cross-reactivity by providing fixed anchor points that enable TCRs to tolerate a variable peptide cargo.	DISCUSS
40	43	TCR	complex_assembly	Alternatively, interactions between the TCR and peptide have been shown to dominate the energetic landscape during ligand engagement, ensuring that T cells retain peptide specificity.	DISCUSS
38	45	1E6 TCR	complex_assembly	The binding mechanism utilized by the 1E6 TCR during pMHC recognition is consistent with both of these models.	DISCUSS
53	57	pMHC	complex_assembly	The binding mechanism utilized by the 1E6 TCR during pMHC recognition is consistent with both of these models.	DISCUSS
103	112	GPD motif	structure_element	Ligand engagement is dominated by peptide interactions, but hotspot-like interactions with the central GPD motif enable the 1E6 TCR to tolerate peptide residues that vary outside of this region, explaining how T cells expressing this TCR may cross-react with a large number of different peptides.	DISCUSS
124	131	1E6 TCR	complex_assembly	Ligand engagement is dominated by peptide interactions, but hotspot-like interactions with the central GPD motif enable the 1E6 TCR to tolerate peptide residues that vary outside of this region, explaining how T cells expressing this TCR may cross-react with a large number of different peptides.	DISCUSS
234	237	TCR	complex_assembly	Ligand engagement is dominated by peptide interactions, but hotspot-like interactions with the central GPD motif enable the 1E6 TCR to tolerate peptide residues that vary outside of this region, explaining how T cells expressing this TCR may cross-react with a large number of different peptides.	DISCUSS
70	77	Hy.1B11	protein	These findings are also analogous to the observed binding mode of the Hy.1B11 TCR, in which one aromatic residue of the TCR CDR3α loop anchored into a pocket created by a conserved peptide motif.	DISCUSS
78	81	TCR	complex_assembly	These findings are also analogous to the observed binding mode of the Hy.1B11 TCR, in which one aromatic residue of the TCR CDR3α loop anchored into a pocket created by a conserved peptide motif.	DISCUSS
120	123	TCR	complex_assembly	These findings are also analogous to the observed binding mode of the Hy.1B11 TCR, in which one aromatic residue of the TCR CDR3α loop anchored into a pocket created by a conserved peptide motif.	DISCUSS
124	134	CDR3α loop	structure_element	These findings are also analogous to the observed binding mode of the Hy.1B11 TCR, in which one aromatic residue of the TCR CDR3α loop anchored into a pocket created by a conserved peptide motif.	DISCUSS
59	62	TCR	complex_assembly	In both of these examples, self-recognition is mediated by TCR residues with aromatic side chains.	DISCUSS
84	94	CDR2 loops	structure_element	Combined with evidence demonstrating that aromatic side chains are conserved in the CDR2 loops of TCRs from many species, we speculate that these aromatic residues could impart a level of “stickiness” to TCRs, which might be enriched in an autoimmune setting when the TCR often binds in a nonoptimal fashion.	DISCUSS
98	102	TCRs	complex_assembly	Combined with evidence demonstrating that aromatic side chains are conserved in the CDR2 loops of TCRs from many species, we speculate that these aromatic residues could impart a level of “stickiness” to TCRs, which might be enriched in an autoimmune setting when the TCR often binds in a nonoptimal fashion.	DISCUSS
204	208	TCRs	complex_assembly	Combined with evidence demonstrating that aromatic side chains are conserved in the CDR2 loops of TCRs from many species, we speculate that these aromatic residues could impart a level of “stickiness” to TCRs, which might be enriched in an autoimmune setting when the TCR often binds in a nonoptimal fashion.	DISCUSS
268	271	TCR	complex_assembly	Combined with evidence demonstrating that aromatic side chains are conserved in the CDR2 loops of TCRs from many species, we speculate that these aromatic residues could impart a level of “stickiness” to TCRs, which might be enriched in an autoimmune setting when the TCR often binds in a nonoptimal fashion.	DISCUSS
54	77	surface complementarity	evidence	Despite some weak statistical correlation between the surface complementarity (SC) and affinity, closer inspection of the interface revealed no obvious structural signature that could definitively explain the differences in antigen potency and TCR binding strength between the different ligands.	DISCUSS
79	81	SC	evidence	Despite some weak statistical correlation between the surface complementarity (SC) and affinity, closer inspection of the interface revealed no obvious structural signature that could definitively explain the differences in antigen potency and TCR binding strength between the different ligands.	DISCUSS
87	95	affinity	evidence	Despite some weak statistical correlation between the surface complementarity (SC) and affinity, closer inspection of the interface revealed no obvious structural signature that could definitively explain the differences in antigen potency and TCR binding strength between the different ligands.	DISCUSS
122	131	interface	site	Despite some weak statistical correlation between the surface complementarity (SC) and affinity, closer inspection of the interface revealed no obvious structural signature that could definitively explain the differences in antigen potency and TCR binding strength between the different ligands.	DISCUSS
224	239	antigen potency	evidence	Despite some weak statistical correlation between the surface complementarity (SC) and affinity, closer inspection of the interface revealed no obvious structural signature that could definitively explain the differences in antigen potency and TCR binding strength between the different ligands.	DISCUSS
244	264	TCR binding strength	evidence	Despite some weak statistical correlation between the surface complementarity (SC) and affinity, closer inspection of the interface revealed no obvious structural signature that could definitively explain the differences in antigen potency and TCR binding strength between the different ligands.	DISCUSS
102	123	central peptide bulge	structure_element	However, similar to our findings in other systems, modifications to residues outside of the canonical central peptide bulge were important for generating new interactions.	DISCUSS
69	72	Arg	residue_name	For example, all of the stronger ligands encoded larger side chains (Arg or Tyr) at peptide position 1 that enabled new interactions with 1E6 not present with the Ala at this position in the natural preproinsulin peptide.	DISCUSS
76	79	Tyr	residue_name	For example, all of the stronger ligands encoded larger side chains (Arg or Tyr) at peptide position 1 that enabled new interactions with 1E6 not present with the Ala at this position in the natural preproinsulin peptide.	DISCUSS
101	102	1	residue_number	For example, all of the stronger ligands encoded larger side chains (Arg or Tyr) at peptide position 1 that enabled new interactions with 1E6 not present with the Ala at this position in the natural preproinsulin peptide.	DISCUSS
163	166	Ala	residue_name	For example, all of the stronger ligands encoded larger side chains (Arg or Tyr) at peptide position 1 that enabled new interactions with 1E6 not present with the Ala at this position in the natural preproinsulin peptide.	DISCUSS
199	212	preproinsulin	protein	For example, all of the stronger ligands encoded larger side chains (Arg or Tyr) at peptide position 1 that enabled new interactions with 1E6 not present with the Ala at this position in the natural preproinsulin peptide.	DISCUSS
213	220	peptide	chemical	For example, all of the stronger ligands encoded larger side chains (Arg or Tyr) at peptide position 1 that enabled new interactions with 1E6 not present with the Ala at this position in the natural preproinsulin peptide.	DISCUSS
69	83	anchor residue	structure_element	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
104	105	2	residue_number	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
107	114	Leu-Gln	mutant	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
139	163	1E6 TCR binding affinity	evidence	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
176	195	structural analysis	experimental_method	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
247	260	A2-AQWGPDPAAA	chemical	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
275	288	A2-ALWGPDPAAA	chemical	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
327	343	binding affinity	evidence	These data also explain our previous findings that alteration of the anchor residue at peptide position 2 (Leu-Gln) has a direct effect on 1E6 TCR binding affinity because our structural analysis demonstrated that 1E6 made 3 additional bonds with A2-AQWGPDPAAA compared with A2-ALWGPDPAAA, consistent with the >3-fold stronger binding affinity.	DISCUSS
56	57	2	residue_number	We have recently demonstrated how a suboptimal position 2 anchor in a melanoma-derived antigen can improve TCR binding through a similar mechanism.	DISCUSS
58	64	anchor	structure_element	We have recently demonstrated how a suboptimal position 2 anchor in a melanoma-derived antigen can improve TCR binding through a similar mechanism.	DISCUSS
107	110	TCR	complex_assembly	We have recently demonstrated how a suboptimal position 2 anchor in a melanoma-derived antigen can improve TCR binding through a similar mechanism.	DISCUSS
94	98	pMHC	complex_assembly	These results challenge the notion that the most potent peptide antigens exhibit the greatest pMHC stability and have implications for the design of anchor residue–modified heteroclitic peptides for vaccination.	DISCUSS
6	28	thermodynamic analysis	experimental_method	Early thermodynamic analysis of TCR-pMHC interactions suggested a common energetic signature, driven by favorable enthalpy (generally mediated through an increase in electrostatic interactions) and unfavorable entropy (changes from disorder to order).	DISCUSS
32	40	TCR-pMHC	complex_assembly	Early thermodynamic analysis of TCR-pMHC interactions suggested a common energetic signature, driven by favorable enthalpy (generally mediated through an increase in electrostatic interactions) and unfavorable entropy (changes from disorder to order).	DISCUSS
114	122	enthalpy	evidence	Early thermodynamic analysis of TCR-pMHC interactions suggested a common energetic signature, driven by favorable enthalpy (generally mediated through an increase in electrostatic interactions) and unfavorable entropy (changes from disorder to order).	DISCUSS
210	217	entropy	evidence	Early thermodynamic analysis of TCR-pMHC interactions suggested a common energetic signature, driven by favorable enthalpy (generally mediated through an increase in electrostatic interactions) and unfavorable entropy (changes from disorder to order).	DISCUSS
35	50	structural data	evidence	These parameters aligned well with structural data, demonstrating that TCRs engaged pMHC using an induced fit binding mode.	DISCUSS
71	75	TCRs	complex_assembly	These parameters aligned well with structural data, demonstrating that TCRs engaged pMHC using an induced fit binding mode.	DISCUSS
84	88	pMHC	complex_assembly	These parameters aligned well with structural data, demonstrating that TCRs engaged pMHC using an induced fit binding mode.	DISCUSS
42	46	TCRs	complex_assembly	However, more recent data have shown that TCRs can utilize a range of energetic strategies during pMHC binding, currently with no obvious pattern in terms of TCR affinity, binding mechanism, or specificity (pathogen, cancer, or self-ligands).	DISCUSS
98	102	pMHC	complex_assembly	However, more recent data have shown that TCRs can utilize a range of energetic strategies during pMHC binding, currently with no obvious pattern in terms of TCR affinity, binding mechanism, or specificity (pathogen, cancer, or self-ligands).	DISCUSS
158	170	TCR affinity	evidence	However, more recent data have shown that TCRs can utilize a range of energetic strategies during pMHC binding, currently with no obvious pattern in terms of TCR affinity, binding mechanism, or specificity (pathogen, cancer, or self-ligands).	DISCUSS
63	67	TCRs	complex_assembly	Although no energetic signature appears to exist for different TCRs, we used thermodynamic analysis here to explore whether changes in energetics could help explain ligand discrimination by a single TCR.	DISCUSS
77	99	thermodynamic analysis	experimental_method	Although no energetic signature appears to exist for different TCRs, we used thermodynamic analysis here to explore whether changes in energetics could help explain ligand discrimination by a single TCR.	DISCUSS
199	202	TCR	complex_assembly	Although no energetic signature appears to exist for different TCRs, we used thermodynamic analysis here to explore whether changes in energetics could help explain ligand discrimination by a single TCR.	DISCUSS
67	97	Pearson’s correlation analysis	experimental_method	This analysis demonstrated a strong relationship (according to the Pearson’s correlation analysis) between the energetic signature used by the 1E6 TCR and the sensitivity of the 1E6 T cell clone to different APLs.	DISCUSS
143	150	1E6 TCR	complex_assembly	This analysis demonstrated a strong relationship (according to the Pearson’s correlation analysis) between the energetic signature used by the 1E6 TCR and the sensitivity of the 1E6 T cell clone to different APLs.	DISCUSS
208	212	APLs	chemical	This analysis demonstrated a strong relationship (according to the Pearson’s correlation analysis) between the energetic signature used by the 1E6 TCR and the sensitivity of the 1E6 T cell clone to different APLs.	DISCUSS
11	14	APL	chemical	The weaker APL ligands were characterized by favorable enthalpy and unfavorable entropy, whereas the stronger ligands progressively shifted to favorable entropy.	DISCUSS
55	63	enthalpy	evidence	The weaker APL ligands were characterized by favorable enthalpy and unfavorable entropy, whereas the stronger ligands progressively shifted to favorable entropy.	DISCUSS
80	87	entropy	evidence	The weaker APL ligands were characterized by favorable enthalpy and unfavorable entropy, whereas the stronger ligands progressively shifted to favorable entropy.	DISCUSS
153	160	entropy	evidence	The weaker APL ligands were characterized by favorable enthalpy and unfavorable entropy, whereas the stronger ligands progressively shifted to favorable entropy.	DISCUSS
80	89	unligated	protein_state	These differences were consistent with a greater degree of movement between the unligated and ligated pMHCs for the weaker ligands, suggesting a greater requirement for disorder-to-order changes during TCR binding.	DISCUSS
94	101	ligated	protein_state	These differences were consistent with a greater degree of movement between the unligated and ligated pMHCs for the weaker ligands, suggesting a greater requirement for disorder-to-order changes during TCR binding.	DISCUSS
102	107	pMHCs	complex_assembly	These differences were consistent with a greater degree of movement between the unligated and ligated pMHCs for the weaker ligands, suggesting a greater requirement for disorder-to-order changes during TCR binding.	DISCUSS
202	205	TCR	complex_assembly	These differences were consistent with a greater degree of movement between the unligated and ligated pMHCs for the weaker ligands, suggesting a greater requirement for disorder-to-order changes during TCR binding.	DISCUSS
272	280	ΔG value	evidence	Thus, the enhanced antigen potency was probably mediated through a shift from an induced fit to a lock-and-key interaction between the stronger ligands (less requirement for energetically unfavorable disorder-to-order changes), resulting in a more energetically favorable ΔG value.	DISCUSS
17	30	preproinsulin	protein	Importantly, the preproinsulin-derived epitope was one of the least potent peptides, demonstrating that the 1E6 T cell clone had the ability to respond to different peptide sequences with far greater potency.	DISCUSS
4	14	RQFGPDWIVA	chemical	The RQFGPDWIVA peptide, which was substantially more potent than the preproinsulin peptide, is within the proteome of a common human pathogen (C. asparagiforme), demonstrating the potential for an encounter between a naive 1E6-like T cell and a foreign peptide with a more potent ligand that might then break self-tolerance.	DISCUSS
69	82	preproinsulin	protein	The RQFGPDWIVA peptide, which was substantially more potent than the preproinsulin peptide, is within the proteome of a common human pathogen (C. asparagiforme), demonstrating the potential for an encounter between a naive 1E6-like T cell and a foreign peptide with a more potent ligand that might then break self-tolerance.	DISCUSS
127	132	human	species	The RQFGPDWIVA peptide, which was substantially more potent than the preproinsulin peptide, is within the proteome of a common human pathogen (C. asparagiforme), demonstrating the potential for an encounter between a naive 1E6-like T cell and a foreign peptide with a more potent ligand that might then break self-tolerance.	DISCUSS
143	159	C. asparagiforme	species	The RQFGPDWIVA peptide, which was substantially more potent than the preproinsulin peptide, is within the proteome of a common human pathogen (C. asparagiforme), demonstrating the potential for an encounter between a naive 1E6-like T cell and a foreign peptide with a more potent ligand that might then break self-tolerance.	DISCUSS
81	86	human	species	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
87	92	viral	taxonomy_domain	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
133	142	conserved	protein_state	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
151	160	GPD motif	structure_element	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
165	180	anchor residues	structure_element	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
194	195	2	residue_number	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
200	202	10	residue_number	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
232	243	HLA-A*02:01	protein	Indeed, we found over 50 decamer peptides from the proteome of likely, or known, human viral pathogens alone that contained both the conserved central GPD motif and anchor residues at positions 2 and 10 that would enable binding to HLA-A*02:01.	DISCUSS
83	88	human	species	Further experiments will be required to determine whether any naturally presented, human pathogen–derived peptides act as active ligands for 1E6, but our work presented here demonstrates that it is at least feasible for an autoimmune TCR to bind to a different peptide sequence that could be present in a pathogen proteome with substantially higher affinity and potency than the interaction it might use to attack self-tissue.	DISCUSS
234	237	TCR	complex_assembly	Further experiments will be required to determine whether any naturally presented, human pathogen–derived peptides act as active ligands for 1E6, but our work presented here demonstrates that it is at least feasible for an autoimmune TCR to bind to a different peptide sequence that could be present in a pathogen proteome with substantially higher affinity and potency than the interaction it might use to attack self-tissue.	DISCUSS
349	357	affinity	evidence	Further experiments will be required to determine whether any naturally presented, human pathogen–derived peptides act as active ligands for 1E6, but our work presented here demonstrates that it is at least feasible for an autoimmune TCR to bind to a different peptide sequence that could be present in a pathogen proteome with substantially higher affinity and potency than the interaction it might use to attack self-tissue.	DISCUSS
150	155	human	species	In summary, this investigation into the molecular basis of T cell cross-reactivity using a clinically relevant cytotoxic CD8+ T cell clone that kills human pancreatic β cells provides answers to a number of previously outstanding questions.	DISCUSS
36	39	TCR	complex_assembly	First, our data shows that a single TCR has the potential to functionally (assessed through T cell activation) bind to different ligands with affinities ranging across 3 orders of magnitude.	DISCUSS
142	152	affinities	evidence	First, our data shows that a single TCR has the potential to functionally (assessed through T cell activation) bind to different ligands with affinities ranging across 3 orders of magnitude.	DISCUSS
96	101	human	species	Second, this is the first example in which ligands have been identified and characterized for a human autoreactive TCR that are substantially more potent than the natural self-ligand, demonstrating the potential for a pathogenic ligand to break self-tolerance and prime self-reactive T cells.	DISCUSS
115	118	TCR	complex_assembly	Second, this is the first example in which ligands have been identified and characterized for a human autoreactive TCR that are substantially more potent than the natural self-ligand, demonstrating the potential for a pathogenic ligand to break self-tolerance and prime self-reactive T cells.	DISCUSS
18	37	structural analysis	experimental_method	Third, this first structural analysis of a cross-reactive human MHCI–restricted autoimmune TCR showed that degeneracy was mediated through TCR-pMHC anchoring by a conserved minimal binding peptide motif.	DISCUSS
58	63	human	species	Third, this first structural analysis of a cross-reactive human MHCI–restricted autoimmune TCR showed that degeneracy was mediated through TCR-pMHC anchoring by a conserved minimal binding peptide motif.	DISCUSS
64	68	MHCI	complex_assembly	Third, this first structural analysis of a cross-reactive human MHCI–restricted autoimmune TCR showed that degeneracy was mediated through TCR-pMHC anchoring by a conserved minimal binding peptide motif.	DISCUSS
91	94	TCR	complex_assembly	Third, this first structural analysis of a cross-reactive human MHCI–restricted autoimmune TCR showed that degeneracy was mediated through TCR-pMHC anchoring by a conserved minimal binding peptide motif.	DISCUSS
139	147	TCR-pMHC	complex_assembly	Third, this first structural analysis of a cross-reactive human MHCI–restricted autoimmune TCR showed that degeneracy was mediated through TCR-pMHC anchoring by a conserved minimal binding peptide motif.	DISCUSS
163	172	conserved	protein_state	Third, this first structural analysis of a cross-reactive human MHCI–restricted autoimmune TCR showed that degeneracy was mediated through TCR-pMHC anchoring by a conserved minimal binding peptide motif.	DISCUSS
173	202	minimal binding peptide motif	structure_element	Third, this first structural analysis of a cross-reactive human MHCI–restricted autoimmune TCR showed that degeneracy was mediated through TCR-pMHC anchoring by a conserved minimal binding peptide motif.	DISCUSS
9	12	TCR	complex_assembly	Finally, TCR ligand discrimination was characterized by an energetic shift from an enthalpically to entropically driven interaction.	DISCUSS
80	93	preproinsulin	protein	Our demonstration of the molecular mechanism governing cross-reactivity by this preproinsulin reactive human CD8+ T cell clone supports the notion first put forward by Wucherpfennig and Strominger that molecular mimicry could mediate autoimmunity and has far-reaching implications for the complex nature of T cell antigen discrimination.	DISCUSS
103	108	human	species	Our demonstration of the molecular mechanism governing cross-reactivity by this preproinsulin reactive human CD8+ T cell clone supports the notion first put forward by Wucherpfennig and Strominger that molecular mimicry could mediate autoimmunity and has far-reaching implications for the complex nature of T cell antigen discrimination.	DISCUSS
62	66	APLs	chemical	The 1E6 T cell clone reacts with a broad sensitivity range to APLs.	FIG
47	69	peptide dilution assay	experimental_method	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
91	101	MVWGPDPLYV	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
110	120	YLGGPDFPTI	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
128	138	ALWGPDPAAA	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
147	157	AQWGPDPAAA	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
167	177	RQFGPDWIVA	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
191	201	RQWGPDPAAV	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
212	222	YQFGPDFPTA	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
237	247	RQFGPDFPTI	chemical	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
277	287	HLA-A*0201	protein	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
324	330	MIP-1β	protein	(A and B) The 1E6 T cell clone was tested in a peptide dilution assay, in triplicate, with MVWGPDPLYV (gray), YLGGPDFPTI (red), ALWGPDPAAA (blue), AQWGPDPAAA (green), RQFGPDWIVA (dark blue), RQWGPDPAAV (purple), YQFGPDFPTA (yellow), and RQFGPDFPTI (cyan) peptides presented by HLA-A*0201–expressing C1R cells for release of MIP-1β (A) and killing (B).	FIG
57	66	tetramers	oligomeric_state	(C) The 1E6 T cell clone was stained, in duplicate, with tetramers composed of each APL (colored as above) presented by HLA-A*0201. (D) The stability of each APL (colored as above) was tested, in duplicate, using CD by recording the peak at 218 nm absorbance from 5°C–90°C.	FIG
84	87	APL	chemical	(C) The 1E6 T cell clone was stained, in duplicate, with tetramers composed of each APL (colored as above) presented by HLA-A*0201. (D) The stability of each APL (colored as above) was tested, in duplicate, using CD by recording the peak at 218 nm absorbance from 5°C–90°C.	FIG
120	130	HLA-A*0201	protein	(C) The 1E6 T cell clone was stained, in duplicate, with tetramers composed of each APL (colored as above) presented by HLA-A*0201. (D) The stability of each APL (colored as above) was tested, in duplicate, using CD by recording the peak at 218 nm absorbance from 5°C–90°C.	FIG
158	161	APL	chemical	(C) The 1E6 T cell clone was stained, in duplicate, with tetramers composed of each APL (colored as above) presented by HLA-A*0201. (D) The stability of each APL (colored as above) was tested, in duplicate, using CD by recording the peak at 218 nm absorbance from 5°C–90°C.	FIG
213	215	CD	experimental_method	(C) The 1E6 T cell clone was stained, in duplicate, with tetramers composed of each APL (colored as above) presented by HLA-A*0201. (D) The stability of each APL (colored as above) was tested, in duplicate, using CD by recording the peak at 218 nm absorbance from 5°C–90°C.	FIG
0	2	Tm	evidence	Tm values were calculated using a Boltzmann fit to each set of data.	FIG
34	67	Boltzmann fit to each set of data	experimental_method	Tm values were calculated using a Boltzmann fit to each set of data.	FIG
0	26	3D and 2D binding analysis	experimental_method	3D and 2D binding analysis of the 1E6 TCR with A2-ALW and the APLs.	FIG
34	41	1E6 TCR	complex_assembly	3D and 2D binding analysis of the 1E6 TCR with A2-ALW and the APLs.	FIG
47	53	A2-ALW	chemical	3D and 2D binding analysis of the 1E6 TCR with A2-ALW and the APLs.	FIG
62	66	APLs	chemical	3D and 2D binding analysis of the 1E6 TCR with A2-ALW and the APLs.	FIG
6	22	Binding affinity	evidence	(A–H) Binding affinity of the 1E6 TCR interaction at 25°C using SPR.	FIG
30	37	1E6 TCR	complex_assembly	(A–H) Binding affinity of the 1E6 TCR interaction at 25°C using SPR.	FIG
64	67	SPR	experimental_method	(A–H) Binding affinity of the 1E6 TCR interaction at 25°C using SPR.	FIG
30	37	1E6 TCR	complex_assembly	Eight serial dilutions of the 1E6 TCR were measured (shown in the inset); representative data from 3 independent experiments are plotted.	FIG
4	32	equilibrium binding constant	evidence	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y= [P1x]/[P2 + X]).	FIG
34	36	KD	evidence	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y= [P1x]/[P2 + X]).	FIG
69	88	nonlinear curve fit	experimental_method	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y= [P1x]/[P2 + X]).	FIG
41	48	1E6 TCR	complex_assembly	In order to calculate each response, the 1E6 TCR was also injected over a control sample (HLA-A*0201–ILAKFLHWL) that was deducted from the experimental data.	FIG
90	110	HLA-A*0201–ILAKFLHWL	complex_assembly	In order to calculate each response, the 1E6 TCR was also injected over a control sample (HLA-A*0201–ILAKFLHWL) that was deducted from the experimental data.	FIG
4	21	1E6-A2-MVWGPDPLYV	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
47	64	1E6-A2-YLGGPDFPTI	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
90	107	1E6-A2-ALWGPDPAAA	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
113	130	1E6-A2-AQWGPDPAAA	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
136	153	1E6-A2-RQFGPDWIVA	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
159	176	1E6-A2-RQWGPDPAAV	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
182	199	1E6-A2-YQFGPDFPTA	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
209	226	1E6-A2-RQFGPDFPTI	complex_assembly	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
232	241	ΔG values	evidence	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
259	262	SPR	experimental_method	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
294	298	EC50	evidence	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
396	426	Pearson’s coefficient analysis	experimental_method	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
428	429	r	evidence	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
435	436	P	evidence	(A) 1E6-A2-MVWGPDPLYV (approximate value); (B) 1E6-A2-YLGGPDFPTI (approximate value); (C) 1E6-A2-ALWGPDPAAA; (D) 1E6-A2-AQWGPDPAAA; (E) 1E6-A2-RQFGPDWIVA; (F) 1E6-A2-RQWGPDPAAV; (G) 1E6-A2-YQFGPDFPTA; and (H) 1E6-A2-RQFGPDFPTI. (I) ΔG values, calculated from SPR experiments, plotted against 1/EC50 (the reciprocal peptide concentration required to reach half-maximal 1E6 T cell killing) showing Pearson’s coefficient analysis (r) and P value (including approximate values from A and B).	FIG
4	25	Effective 2D affinity	evidence	(J) Effective 2D affinity (AcKa) calculated using adhesion frequency assays, using at least 5 cell pairs, and calculated as an average of 100 cell cell contacts.	FIG
27	31	AcKa	evidence	(J) Effective 2D affinity (AcKa) calculated using adhesion frequency assays, using at least 5 cell pairs, and calculated as an average of 100 cell cell contacts.	FIG
50	75	adhesion frequency assays	experimental_method	(J) Effective 2D affinity (AcKa) calculated using adhesion frequency assays, using at least 5 cell pairs, and calculated as an average of 100 cell cell contacts.	FIG
4	25	Effective 2D affinity	evidence	(K) Effective 2D affinity plotted against 1/EC50 showing Pearson’s coefficient analysis (r) and P value.	FIG
44	48	EC50	evidence	(K) Effective 2D affinity plotted against 1/EC50 showing Pearson’s coefficient analysis (r) and P value.	FIG
57	87	Pearson’s coefficient analysis	experimental_method	(K) Effective 2D affinity plotted against 1/EC50 showing Pearson’s coefficient analysis (r) and P value.	FIG
89	90	r	evidence	(K) Effective 2D affinity plotted against 1/EC50 showing Pearson’s coefficient analysis (r) and P value.	FIG
96	103	P value	evidence	(K) Effective 2D affinity plotted against 1/EC50 showing Pearson’s coefficient analysis (r) and P value.	FIG
4	11	1E6 TCR	complex_assembly	The 1E6 TCR uses a conserved binding mode to engage A2-ALWGPDPAAA and the APLs.	FIG
52	65	A2-ALWGPDPAAA	chemical	The 1E6 TCR uses a conserved binding mode to engage A2-ALWGPDPAAA and the APLs.	FIG
74	78	APLs	chemical	The 1E6 TCR uses a conserved binding mode to engage A2-ALWGPDPAAA and the APLs.	FIG
4	17	Superposition	experimental_method	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
25	32	1E6 TCR	complex_assembly	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
61	76	in complex with	protein_state	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
83	87	APLs	chemical	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
118	131	A2-ALWGPDPAAA	chemical	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
149	159	HLA-A*0201	protein	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
192	197	align	experimental_method	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
209	219	structures	evidence	(A) Superposition of the 1E6 TCR (multicolored illustration) in complex with all 7 APLs (multicolored sticks) and the A2-ALWGPDPAAA ligand using the HLA-A*0201 (gray illustration) molecule to align all of the structures.	FIG
4	11	1E6 TCR	complex_assembly	The 1E6 TCR and each peptide are colored according to the APL used in the complex as in Figure 1. (B) Position of the 1E6 TCR CDR loops (multicolored lines) in each complex.	FIG
58	61	APL	chemical	The 1E6 TCR and each peptide are colored according to the APL used in the complex as in Figure 1. (B) Position of the 1E6 TCR CDR loops (multicolored lines) in each complex.	FIG
118	125	1E6 TCR	complex_assembly	The 1E6 TCR and each peptide are colored according to the APL used in the complex as in Figure 1. (B) Position of the 1E6 TCR CDR loops (multicolored lines) in each complex.	FIG
126	135	CDR loops	structure_element	The 1E6 TCR and each peptide are colored according to the APL used in the complex as in Figure 1. (B) Position of the 1E6 TCR CDR loops (multicolored lines) in each complex.	FIG
4	14	ALWGPDPAAA	chemical	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
54	79	HLA-A*0201 binding groove	site	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
137	140	APL	chemical	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
191	201	HLA-A*0201	protein	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
202	212	α1 helices	structure_element	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
238	252	Crossing angle	evidence	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
260	267	1E6 TCR	complex_assembly	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
360	370	ALWGPDPAAA	chemical	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
394	402	bound in	protein_state	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
407	432	HLA-A*0201 binding groove	site	The ALWGPDPAAA peptide (green sticks) is shown in the HLA-A*0201 binding groove (gray surface). (C) The Cα backbone conformation of each APL (multicolored illustration) in the context of the HLA-A*0201 α1 helices (gray illustration). (D) Crossing angle of the 1E6 TCR (multicolored lines) calculated using previously published parameters in the context of the ALWGPDPAAA peptide (green sticks) bound in the HLA-A*0201 binding groove (gray surface).	FIG
31	40	GPD motif	structure_element	A conserved interaction with a GPD motif underpins the 1E6 TCR interaction with the APLs.	FIG
55	62	1E6 TCR	complex_assembly	A conserved interaction with a GPD motif underpins the 1E6 TCR interaction with the APLs.	FIG
84	88	APLs	chemical	A conserved interaction with a GPD motif underpins the 1E6 TCR interaction with the APLs.	FIG
20	27	1E6 TCR	complex_assembly	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
57	63	Tyr97α	residue_name_number	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
68	74	Tyr97β	residue_name_number	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
117	120	TCR	complex_assembly	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
121	136	in complex with	protein_state	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
143	147	APLs	chemical	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
177	190	A2-ALWGPDPAAA	chemical	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
247	264	GPD peptide motif	structure_element	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
309	313	APLs	chemical	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
318	331	A2-ALWGPDPAAA	chemical	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
332	347	in complex with	protein_state	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
352	359	1E6 TCR	complex_assembly	Interaction between 1E6 TCR (gray illustration) residues Tyr97α and Tyr97β (the position of these side chains in the TCR in complex with all 7 APLs, and the previously reported A2-ALWGPDPAAA epitope, is shown in multicolored sticks; ref.) and the GPD peptide motif (the position of these side chains in all 7 APLs and A2-ALWGPDPAAA in complex with the 1E6 TCR is shown in multicolored sticks).	FIG
33	36	MHC	complex_assembly	The rest of the peptide, and the MHCα1 helix, are shown as a gray illustration.	FIG
36	44	α1 helix	structure_element	The rest of the peptide, and the MHCα1 helix, are shown as a gray illustration.	FIG
4	11	1E6 TCR	complex_assembly	The 1E6 TCR makes distinct peptide contacts with peripheral APL residues.	FIG
60	63	APL	chemical	The 1E6 TCR makes distinct peptide contacts with peripheral APL residues.	FIG
25	32	1E6 TCR	complex_assembly	Interactions between the 1E6 TCR and peptide residues outside of the conserved GPD motif.	FIG
69	78	conserved	protein_state	Interactions between the 1E6 TCR and peptide residues outside of the conserved GPD motif.	FIG
79	88	GPD motif	structure_element	Interactions between the 1E6 TCR and peptide residues outside of the conserved GPD motif.	FIG
4	7	MHC	complex_assembly	The MHCα1 helix is shown in gray illustrations.	FIG
7	15	α1 helix	structure_element	The MHCα1 helix is shown in gray illustrations.	FIG
0	14	Hydrogen bonds	bond_interaction	Hydrogen bonds are shown as red dotted lines; van der Waals (vdW) contacts are shown as black dotted lines.	FIG
46	74	van der Waals (vdW) contacts	bond_interaction	Hydrogen bonds are shown as red dotted lines; van der Waals (vdW) contacts are shown as black dotted lines.	FIG
38	45	1E6 TCR	complex_assembly	Boxes show total contacts between the 1E6 TCR and each peptide ligand.	FIG
28	35	1E6 TCR	complex_assembly	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
72	85	A2-MVWGPDPLYV	chemical	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
147	154	1E6 TCR	complex_assembly	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
189	202	A2-YLGGPDFPTI	chemical	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
262	269	1E6 TCR	complex_assembly	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
305	318	A2-ALWGPDPAAA	chemical	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
28	35	1E6 TCR	complex_assembly	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
72	85	A2-MVWGPDPLYV	chemical	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
147	154	1E6 TCR	complex_assembly	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
189	202	A2-YLGGPDFPTI	chemical	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
262	269	1E6 TCR	complex_assembly	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
305	318	A2-ALWGPDPAAA	chemical	(A) Interaction between the 1E6 TCR (black illustration and sticks) and A2-MVWGPDPLYV (black illustration and sticks). (B) Interaction between the 1E6 TCR (red illustration and sticks) and A2-YLGGPDFPTI (red illustration and sticks). (C) Interaction between the 1E6 TCR (blue illustration and sticks) and A2-ALWGPDPAAA (blue illustration and sticks) reproduced from previous published data.	FIG
28	35	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
72	85	A2-AQWGPDPAAA	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
147	154	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
195	208	A2-RQFGPDWIVA	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
274	281	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
319	332	A2-RQWGPDPAAV	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
395	402	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
440	453	A2-YQFGPDFPTA	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
516	523	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
559	572	A2-RQFGPDFPTI	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
28	35	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
72	85	A2-AQWGPDPAAA	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
147	154	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
195	208	A2-RQFGPDWIVA	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
274	281	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
319	332	A2-RQWGPDPAAV	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
395	402	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
440	453	A2-YQFGPDFPTA	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
516	523	1E6 TCR	complex_assembly	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
559	572	A2-RQFGPDFPTI	chemical	(D) Interaction between the 1E6 TCR (green illustration and sticks) and A2-AQWGPDPAAA (green illustration and sticks). (E) Interaction between the 1E6 TCR (dark blue illustration and sticks) and A2-RQFGPDWIVA (dark blue illustration and sticks). (F) Interaction between the 1E6 TCR (purple illustration and sticks) and A2-RQWGPDPAAV (purple illustration and sticks). (G) Interaction between the 1E6 TCR (yellow illustration and sticks) and A2-YQFGPDFPTA (yellow illustration and sticks). (H) Interaction between the 1E6 TCR (cyan illustration and sticks) and A2-RQFGPDFPTI (cyan illustration and sticks).	FIG
14	21	ligated	protein_state	Comparison of ligated and unligated APLs.	FIG
26	35	unligated	protein_state	Comparison of ligated and unligated APLs.	FIG
36	40	APLs	chemical	Comparison of ligated and unligated APLs.	FIG
0	13	Superposition	experimental_method	Superposition of each APL in unligated form and ligated to the 1E6 TCR.	FIG
22	25	APL	chemical	Superposition of each APL in unligated form and ligated to the 1E6 TCR.	FIG
29	38	unligated	protein_state	Superposition of each APL in unligated form and ligated to the 1E6 TCR.	FIG
48	55	ligated	protein_state	Superposition of each APL in unligated form and ligated to the 1E6 TCR.	FIG
63	70	1E6 TCR	complex_assembly	Superposition of each APL in unligated form and ligated to the 1E6 TCR.	FIG
4	13	unligated	protein_state	All unligated pMHCs are shown as light green illustrations.	FIG
14	19	pMHCs	complex_assembly	All unligated pMHCs are shown as light green illustrations.	FIG
44	53	structure	evidence	Peptide sequences are shown underneath each structure aligned with the peptide structure.	FIG
79	88	structure	evidence	Peptide sequences are shown underneath each structure aligned with the peptide structure.	FIG
4	17	A2-MVWGPDPLYV	chemical	(A) A2-MVWGPDPLYV (black sticks).	FIG
46	50	Tyr8	residue_name_number	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
58	65	ligated	protein_state	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
73	82	unligated	protein_state	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
110	123	A2-YLGGPDFPTI	chemical	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
142	155	A2-ALWGPDPAAA	chemical	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
215	228	A2-AQWGPDPAAA	chemical	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
249	262	A2-RQFGPDWIVA	chemical	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
287	300	A2-RQWGPDPAAV	chemical	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
322	335	A2-YQFGPDFPTA	chemical	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
357	370	A2-RQFGPDFPTI	chemical	A large conformational shift was observed for Tyr8 in the ligated versus unligated states (black circle). (B) A2-YLGGPDFPTI (red sticks). (C) A2-ALWGPDPAAA (blue sticks) reproduced from previous published data. (D) A2-AQWGPDPAAA (green sticks). (E) A2-RQFGPDWIVA (dark blue sticks). (F) A2-RQWGPDPAAV (purple sticks). (G) A2-YQFGPDFPTA (yellow sticks). (H) A2-RQFGPDFPTI (cyan sticks).	FIG
4	11	1E6 TCR	complex_assembly	The 1E6 TCR makes distinct peptide contacts with the MHC surface depending on the peptide cargo.	FIG
53	64	MHC surface	site	The 1E6 TCR makes distinct peptide contacts with the MHC surface depending on the peptide cargo.	FIG
25	32	1E6 TCR	complex_assembly	Interactions between the 1E6 TCR and the MHC α1 helix residues Arg65, Lys66, and Gln72.	FIG
41	44	MHC	complex_assembly	Interactions between the 1E6 TCR and the MHC α1 helix residues Arg65, Lys66, and Gln72.	FIG
45	53	α1 helix	structure_element	Interactions between the 1E6 TCR and the MHC α1 helix residues Arg65, Lys66, and Gln72.	FIG
63	68	Arg65	residue_name_number	Interactions between the 1E6 TCR and the MHC α1 helix residues Arg65, Lys66, and Gln72.	FIG
70	75	Lys66	residue_name_number	Interactions between the 1E6 TCR and the MHC α1 helix residues Arg65, Lys66, and Gln72.	FIG
81	86	Gln72	residue_name_number	Interactions between the 1E6 TCR and the MHC α1 helix residues Arg65, Lys66, and Gln72.	FIG
0	14	Hydrogen bonds	bond_interaction	Hydrogen bonds are shown as red dotted lines; vdW contacts are shown as black dotted lines.	FIG
46	49	vdW	bond_interaction	Hydrogen bonds are shown as red dotted lines; vdW contacts are shown as black dotted lines.	FIG
0	3	MHC	complex_assembly	MHCα1 helix are shown in gray illustrations.	FIG
3	11	α1 helix	structure_element	MHCα1 helix are shown in gray illustrations.	FIG
38	45	1E6 TCR	complex_assembly	Boxes show total contacts between the 1E6 TCR and these key residues (green boxes are MHC residues; white boxes are TCR residues).	FIG
86	89	MHC	complex_assembly	Boxes show total contacts between the 1E6 TCR and these key residues (green boxes are MHC residues; white boxes are TCR residues).	FIG
116	119	TCR	complex_assembly	Boxes show total contacts between the 1E6 TCR and these key residues (green boxes are MHC residues; white boxes are TCR residues).	FIG
0	22	Thermodynamic analysis	experimental_method	Thermodynamic analysis of the 1E6 TCR with A2-ALWGPDPAAA and the APLs.	FIG
30	37	1E6 TCR	complex_assembly	Thermodynamic analysis of the 1E6 TCR with A2-ALWGPDPAAA and the APLs.	FIG
43	56	A2-ALWGPDPAAA	chemical	Thermodynamic analysis of the 1E6 TCR with A2-ALWGPDPAAA and the APLs.	FIG
65	69	APLs	chemical	Thermodynamic analysis of the 1E6 TCR with A2-ALWGPDPAAA and the APLs.	FIG
30	37	1E6 TCR	complex_assembly	Eight serial dilutions of the 1E6 TCR were injected, in duplicate, over each immobilized APL and A2-ALW at 5°C, 13°C, 18°C, 25°C, 30°C, and 37°C.	FIG
89	92	APL	chemical	Eight serial dilutions of the 1E6 TCR were injected, in duplicate, over each immobilized APL and A2-ALW at 5°C, 13°C, 18°C, 25°C, 30°C, and 37°C.	FIG
97	103	A2-ALW	chemical	Eight serial dilutions of the 1E6 TCR were injected, in duplicate, over each immobilized APL and A2-ALW at 5°C, 13°C, 18°C, 25°C, 30°C, and 37°C.	FIG
4	32	equilibrium binding constant	evidence	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y = [P1x]/[P2 + X]), and thermodynamic parameters were calculated according to the Gibbs-Helmholtz equation (ΔG° = ΔH − TΔS°).	FIG
34	36	KD	evidence	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y = [P1x]/[P2 + X]), and thermodynamic parameters were calculated according to the Gibbs-Helmholtz equation (ΔG° = ΔH − TΔS°).	FIG
69	88	nonlinear curve fit	experimental_method	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y = [P1x]/[P2 + X]), and thermodynamic parameters were calculated according to the Gibbs-Helmholtz equation (ΔG° = ΔH − TΔS°).	FIG
173	197	Gibbs-Helmholtz equation	experimental_method	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y = [P1x]/[P2 + X]), and thermodynamic parameters were calculated according to the Gibbs-Helmholtz equation (ΔG° = ΔH − TΔS°).	FIG
199	202	ΔG°	evidence	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y = [P1x]/[P2 + X]), and thermodynamic parameters were calculated according to the Gibbs-Helmholtz equation (ΔG° = ΔH − TΔS°).	FIG
205	207	ΔH	evidence	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y = [P1x]/[P2 + X]), and thermodynamic parameters were calculated according to the Gibbs-Helmholtz equation (ΔG° = ΔH − TΔS°).	FIG
210	214	TΔS°	evidence	The equilibrium binding constant (KD) values were calculated using a nonlinear curve fit (y = [P1x]/[P2 + X]), and thermodynamic parameters were calculated according to the Gibbs-Helmholtz equation (ΔG° = ΔH − TΔS°).	FIG
4	25	binding free energies	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
27	30	ΔG°	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
32	35	ΔG°	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
90	110	nonlinear regression	experimental_method	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
135	154	van’t Hoff equation	experimental_method	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
156	164	RT ln KD	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
167	170	ΔH°	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
173	177	TΔS°	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
180	184	ΔCp°	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
193	198	TΔCp°	evidence	The binding free energies, ΔG° (ΔG° = RTlnKD), were plotted against temperature (K) using nonlinear regression to fit the 3-parameters van’t Hoff equation (RT ln KD = ΔH° – TΔS° + ΔCp°[T-T0] – TΔCp° ln [T/T0] with T0 = 298 K).	FIG
4	21	1E6-A2-ALWGPDPAAA	complex_assembly	(A) 1E6-A2-ALWGPDPAAA; (B) 1E6-A2-AQWGPDPAAA; (C) 1E6-A2-RQFGPDWIVA; (D) 1E6-A2-RQWGPDPAAV, (E) 1E6-A2-YQFGPDFPTA; and (F) 1E6-A2-RQFGPDFPTI.	FIG
27	44	1E6-A2-AQWGPDPAAA	complex_assembly	(A) 1E6-A2-ALWGPDPAAA; (B) 1E6-A2-AQWGPDPAAA; (C) 1E6-A2-RQFGPDWIVA; (D) 1E6-A2-RQWGPDPAAV, (E) 1E6-A2-YQFGPDFPTA; and (F) 1E6-A2-RQFGPDFPTI.	FIG
50	67	1E6-A2-RQFGPDWIVA	complex_assembly	(A) 1E6-A2-ALWGPDPAAA; (B) 1E6-A2-AQWGPDPAAA; (C) 1E6-A2-RQFGPDWIVA; (D) 1E6-A2-RQWGPDPAAV, (E) 1E6-A2-YQFGPDFPTA; and (F) 1E6-A2-RQFGPDFPTI.	FIG
73	90	1E6-A2-RQWGPDPAAV	complex_assembly	(A) 1E6-A2-ALWGPDPAAA; (B) 1E6-A2-AQWGPDPAAA; (C) 1E6-A2-RQFGPDWIVA; (D) 1E6-A2-RQWGPDPAAV, (E) 1E6-A2-YQFGPDFPTA; and (F) 1E6-A2-RQFGPDFPTI.	FIG
96	113	1E6-A2-YQFGPDFPTA	complex_assembly	(A) 1E6-A2-ALWGPDPAAA; (B) 1E6-A2-AQWGPDPAAA; (C) 1E6-A2-RQFGPDWIVA; (D) 1E6-A2-RQWGPDPAAV, (E) 1E6-A2-YQFGPDFPTA; and (F) 1E6-A2-RQFGPDFPTI.	FIG
123	140	1E6-A2-RQFGPDFPTI	complex_assembly	(A) 1E6-A2-ALWGPDPAAA; (B) 1E6-A2-AQWGPDPAAA; (C) 1E6-A2-RQFGPDWIVA; (D) 1E6-A2-RQWGPDPAAV, (E) 1E6-A2-YQFGPDFPTA; and (F) 1E6-A2-RQFGPDFPTI.	FIG
0	12	1E6 TCR-pMHC	complex_assembly	1E6 TCR-pMHC contacts, affinity measurements and thermodynamics	TABLE
23	44	affinity measurements	experimental_method	1E6 TCR-pMHC contacts, affinity measurements and thermodynamics	TABLE
49	63	thermodynamics	experimental_method	1E6 TCR-pMHC contacts, affinity measurements and thermodynamics	TABLE