bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of two promiscuous T cell epitopes from tetanus toxin
Authors: Ho Paul C. , Mutch David A. , Winkel Ken D. , Saul Allan J. , Jones Graham L. , Doran Trevor J. , Rzepczyk Christine M. 
Published: March 2007

AbstractTetanus toxoid‐specific T cell clones were isolated from a human donor. To determine the T cell epitopes recognized by the clones, 30 peptides representing amphipathic alpha helical regions of the tetanus toxin were screened for ability to induce proliferation of the clones. Two T epitopes were identified. These occurred within peptides 12 and 21, and had the amino acid sequences NSVDDALINSTKIYSYFPSV and PGINGKAIHLVNNESSE, respectively. An unusual feature was that both peptides could be presented to their respective T cell clones by antigen‐presenting cells of many HLA specificities. Further investigation of peptide 12 showed that the epitope was only seven amino acids in length and had a very hydrophobic sequence, namely YSYFPSV. The ability of the T cell epitope‐containing peptides 12 and 21 to interact with many different HLA alleles means they may potentially be very useful as “universal carrier molecules” in synthetic vaccines.
The peritoneal Ly‐1 (CD5) B cell repertoire is unique among murine B cell repertoires
Authors: Lalor Paul A. , Morahan Grant 
Published: March 2007

AbstractLy‐1 (CD5) B cells and conventional B cells represent two distinct lineages of murine B cells which are distinguishable by expression of surface molecules, organ location, ontogeny and development and antibody production in vivo. In order to assess whether the different developmental pathways of Ly‐1 B cells and conventional B cells result in different antibody repertoires, we have used limiting dilution analyses to determine frequencies of B cells making antibodies capable of binding to a range of antigens including haptens, proteins, bacterial polysaccharides and bromelain‐treated mouse red blood cells. Starting populations of B cells were purified from spleen, peritoneum and bone marrow of adult BALB/c mice or from spleens of newborn mice by use of the fluoresence‐activated cell sorter. The peritoneal Ly‐1 B cell repertoire was found to be different from that of conventional B cells, with between 5‐ and 100‐fold higher frequencies of clones producing IgM antibodies capable of binding to the antigens tested. However, when tested, the majority of Ly‐1 B cell anti‐haptenic antibodies did not show the high affinity binding or fine specificity characteristics of specific antibodies elicited in immune responses in vivo. The high frequencies of antigen‐reactive antibodies within the Ly‐1 B repertoire are most likely explained by the presence of clones secreting low‐affinity or multireactive antibodies. The Ly‐1 B cell repertoire is not mirrored in repertoires from either newborn B cells or virgin B cells in adult bone marrow. Therefore, either Ly‐1 B cells develop from distinct precursors with intrinsically different mechanisms of V gene usage and recombination, or newly formed Ly‐1 B are heavily selected on specificity for entry into this peritoneal lineage. If the second alternative is true, bacterial antigens in the gut are not required for selection of this unique repertoire, as Ly‐1 B cells in germ‐free mice also show the multireactive repertoire characteristic of this B cell lineage in normal mice.
Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell‐mediated immunity
Authors: Lider Ofer , Mekori Yoseph A. , Miller Ted , Bar‐Tana Ruth , Vlodavsky Israel , Baharav Ehud , Cohen Irun R. , Naparstek Yaakov 
Published: March 2007

AbstractPreviously we reported that activated T lymphocytes express a heparanase enzyme that degrades the heparan sulfate moiety of the proteoglycan of the extracellular matrix (ECM). Expression of the heparanase enzyme was found to be associated with the ability of activated T lymphocytes to penetrate blood vessel walls and accumulate in target organs. We recently found that relatively low doses of heparin administered to mice or rats inhibited T cell‐mediated immune reactions. In the present study we investigated the effects in vitro and in vivo of the heparanase inhibitor, heparin, on the expression of T lymphocyte heparanase and on the ability of T lymphocytes to mediate a delayed‐type hypersensitivity (DTH) reaction. We found that heparanase was induced by immunizing mice with antigen in vivo or by activating T lymphocytes with concanavalin A in vitro. Relatively low doses of heparin administered once daily in vivo (5 μg) or present in vitro (0.1 μg/ml) inhibited the expression of heparanase induced by immunization or by concanavalin A incubation. Higher or lower doses of heparin did not have these effects. The same doses of heparin that inhibited expression of heparanase also inhibited the ability of the lymph node cells to migrate to a site of antigen and adoptively produce a DTH reaction. These findings suggest that modulation of cell‐mediated immune reactions may be achieved by relatively low doses of heparin which inhibit expression of T lymphocyte heparanase.
Cytokine‐related syndrome following injection of anti‐CD3 monoclonal antibody: Further evidence for transient in vivo T cell activation
Authors: Ferran Christiane , Sheehan Kathleen , Dy Michel , Schreiber Robert , Merite Sylvie , Landais Paul , Noel Laure‐Hélène , Grau Georges , Bluestone Jeffrey , Bach Jean‐François , Chatenoud Lucienne 
Published: March 2007

AbstractIn vivo injection of the hamster anti‐murine CD3 monoclonal antibody 145 2C11 into BALB/c mice induces a massive systemic release of several cytokines. Very high circulating levels of tumor necrosis factor are detected both by enzyme‐linked immunosorbent assay and L‐929 bioassay 90 min following a single injection of 10 μg/mouse 145 2C11. Peak circulating levels of exclusively T cell‐derived products such as interferon‐γ, interleukin 2 and interleukin 3 are also detected 90 min to 8 h post‐injection. Importantly, this cytokine release is transient since none of these cytokines are still present 12 to 24 h post‐injection.In parallel to cytokine release, 145 2C11‐treated mice (10 μg/mouse) exhibit somnolence, hypomotility (quantified by actimetry), hypothermia, diarrhea and piloerection. At this dosage, the physical reaction is not lethal and reverses in all mice by 48 h post‐injection. Severe but again reversible anatomopathological changes are also observed: massive cellular depletion, necrosis and edema of lymphoid organs, leakage syndrome and inflammatory cell infiltrates of the lung, cell vacuolization, necrosis and vascular congestion of the liver.All these data are similar to the clinical and immunological manifestations of the OKT3‐induced reaction in patients and, thus, provide an invaluable experimental tool to study its mechanisms and explore its prevention.
Sequential appearance of γ/δ‐ and α/β‐bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes
Authors: Ohga Shouichi , Yoshikai Yasunobu , Takeda Yasuyuki , Hiromatsu Kenji , Nomoto Kikuo 
Published: March 2007

AbstractTo search for a potential role of T cell antigen receptor (TcR) γ/β‐bearing cells in host‐defense against Listeria monocytogenes, we analyzed the sequential appearance of γ/δ and α/β T cell in the peritoneal exudate cells (PEC) during an i.p. infection with sublethal dose (2 × 103) of viable Listeria organisms in mice. The PEC on day 1 after the infection consisted of 48% macrophages and 50% lymphocytes, most of which were surface IgM+ (B) cells. The number of PEC increased to the maximal level by day 3. The PEC at this stage contained an appreciable number of CD3+ T cells in addition to a large number of macrophages. Of the CD3+ cells, the proportion of CD4−CD8− cells, most of which expressed no TcR α/β, increased to the maximal level on day 3 after the infection. In correlation with an increased number of CD3+CD4−CD8−TcR α/β− cells, high level of TcR γ/δ chain gene messages was detected in the nonadherent population of the PEC on this stage. On the other hand, the PEC on day 8 contained an increased number of CD4+CD8− and CD4−CD8+ cells which expressed TcR α/β chain on their surface. These results suggest that the γ/δ T cells precede the α/β T cells in appearance during listerial infection. The γ/β T cells may be involved at the first line of the host‐defense against Listeria.
Defective V‐to‐J recombination of T cell receptor γ chain genes in scid mice
Authors: Schuler Walter , Schuler Amelie , Bosma Melvin J. 
Published: March 2007

AbstractThe status of T cell receptor γ chain genes (TcR γ) in 11 spontaneous T cell lymphomas from mice with severe combined immune deficiency (scid) was analyzed. We found that as a result of large abnormal deletions accompanying attempted site‐specific V‐to‐J recombinations, 36 of 47 rearranged TcR γ genes lacked the variable (V) and/or joining (J) region gene segment involved in this attempted recombination. No such deletions were found in T cell lymphomas from normal mice. We interpret our data as indicating a defective V‐to‐J recombination in scid lymphocytes consistent with our earlier observation of faulty D‐to‐J recombination in transformed scid lymphocytes (Schuler et al., Cell 1986. 46: 963). The present results further support the hypothesis that the scid mutation affects a component of the VDJ‐recombinase system used in common by B and T cells to assemble antigen receptor genes.
In rat B lymphocyte genesis sixty percent is lost from the bone marrow at the transition of nondividing pre‐B cell to sIgM+ B lymphocyte, the stage of Ig light chain gene expression
Authors: Deenen Gerrit Jan , Van Balen Iteke , Opstelten Davine 
Published: March 2007

AbstractThe cycling B precursor cells in rat bone marrow (BM) that carry the B220 antigen and no surface Ig daily produce 780 million new cells. The pool of recirculating B lymphocytes in the rat, however, renew at a rate of only about 40 million cells/day. To analyze at which stages in B lymphocyte genesis the cell loss occurs, we identified post‐mitotic cells in the rat BM B lineage, and determined their renewal rates. We used 5‐bromo‐deoxyuridine (BrdUrd) to label DNA‐synthesizing cells, identifying incorporated BrdUrd with the mouse monoclonal antibody BU‐1. B lineage cell subsets were identified by the markers HIS24 antigen (rat B220), terminal deoxynucleotidyl transferase (TdT), Ig μ heavy chain, and complete Ig. By use of double and triple immunocytology, we determined the extent of BrdUrd incorporation in the various B lineage compartments [HIS24+TdT−Ig−, TdT+, cytoplasmic μ chain (cμ)+ surface (s) IgM− pre‐B, sIgM+ B]. Both sIgM+ B lymphocytes and all B precursors with cell diameters < 11–12 μm were virtually devoid of DNA synthesis, as indicated by S‐phase indices below 2%. In contrast, S‐phase indices of large B precursors ranged between 43%–66%.We established the renewal rates of nondividing BM B lineage cells by placing osmotic minipumps containing BrdUrd subcutaneously in the flank of rats. The nondividing BM B lineage cells all renewed rapidly at rates between 2.4% and 5.6%/h, representing average half‐lives of 29 to 12 h. In absolute numbers, the renewal/day/whole body BM was 165 × 106 for sIgM+ B lymphocytes, 422 × 106 for small cμ+ sIgM− pre‐B cells, 89 × 106 for small TdT+ cells and 35 × 106 for small HIS24+TdT−Ig− cells. Assuming that recirculating B lymphocytes in the periphery are the descendants of BM sIgM+ B lymphocytes, which in their turn are the progeny of small pre‐B cells, the renewal data indicate the following. Of the 165 million potentially available BM B lymphocytes, only 40 million cells become incorporated in the pool of recirculating B lymphocytes, representing a loss of 75%. BM B lymphocytes, in turn, use only (165/422 × 100% =) 40% of the potential output from their immediate precursors. The 60% loss that occurs here may reflect the extent of aberrant Ig light chain gene rearrangement in normal B lymphocyte genesis. In the earlier stages in B lymphocyte genesis, many of the 780 × 106 new cells produced by proliferating precursors apparently do not reach the small pre‐B compartment (which takes up only 422 × 106 new cells/day). The overall loss amounts to a total of 95%, with [(780‐165)/780 × 100% =] 80% in the BM and [(165‐40)/780 × 100% =] 15% in the periphery. We discuss mechanisms potentially underlying the loss at the various stages in B lymphocyte development.
Stimulation of lymphocyte migration by a novel low‐molecular weight compound in normal human skin and plasma
Authors: Bacon Kevin B. , Fincham Nicholas J. , Camp Richard D. R. 
Published: March 2007

AbstractNormal human skin contains an extravascular population of lymphocytes which have been proposed to play a central role in immunosurveillance. The hypothesis that physiologic lymphocyte chemoattractants induce the migration of these cells has been tested by analysis of samples from normal human skin by an in vitro lymphocyte migration assay in combination with high‐performance liquid chromatography (HPLC). Dilution‐related lymphocyte migration was seen on assay of aqueous extracts of stratum corneum, analysis after ultrafiltration consistently demonstrating activity in < 1‐kDa fractions. Similar results were obtained with chamber fluid from abraded normal skin and with normal plasma. A novel, polar, low‐molecular weight component in plasma and chamber fluid was purified to homogeneity by reverse‐phase HPLC. Material from the two sources possessed identical retention times on reverse‐phase HPLC and similar ultraviolet (UV) absorbance spectra (UV maximum 274 nm). The factor has been termed plasma‐associated lymphocyte chemoattractant (PALC). When purified to homogeneity, PALC induced concentration‐related lymphocyte migration, was extractable in lipid solvents and was not peptide in nature, as determined by mass spectrometric and amino acid analyses and proteolytic enzyme digestion. It is proposed that PALC may play a role in mediating physiologic margination, adherence and migration of lymphocytes in normal human skin.
Competition among class II major histocompatibility molecules for presentation of tyrosine‐azobenzenearsonate occurs in vivo and in vitro
Authors: Baskar Sivasubramanian , Leskowitz Sidney 
Published: March 2007

AbstractWe have compared by functional assays the relative preference among Ia molecules for their ability to present tyrosine‐azobenzenearsonate (ABA‐Tyr) to T cells. Immunization of B10. BR mice (IAk, IEk) with ABA‐Tyr resulted in the induction of IAk‐restricted T cells only. Immunization of B10.A(5R) mice (IAbb, IEb/k) gave only IEb/k‐restricted T cell clones even though IAb‐restricted responses could be induced in C57BL/6 mice (IAb). These results indicated that IAk was preferred over IEk and IEb/k was preferred over IAb for presentation of ABA‐Tyr. A comparison between IAk and IEb/k made by immunizing [B10.BR × B10.A(5R)]F1 mice (IAk, IEk, IAb, IEb/k), showed that IEb/k was favored over IAk. No IAb‐ or IEk‐restricted response was seen.Further attempts were made to compare Ia preference for ABA‐Tyr presentation by competitive inhibition assays. It could be shown that the presence of IEb/k molecules on an accessory cell interfered with the ability of IAb molecules on the same cell to present ABA‐Tyr to an IAb‐restricted T cell clone by direct competition. Such a competition was not observed between IAk and IEk. Finally, it could be shown that addition of ABA‐Tyr inhibited the presentation of moth cytochrome‐c peptide (81–103) by IEb/k but did not influence its presentation by IEk. From these functional studies we suggest that the binding affinity of ABA‐Tyr with the Ia molecules will fall in the order: IEb/k > IAk > IAb > IEk.
Different response of TH1 cells for stimulation with anti‐CD3 antibodies
Authors: Lohoff Michael , Schmitt Edgar , Reske‐Kunz Angelika B. , Röllinghoff Martin 
Published: March 2007

AbstractIn this report, evidence is provided for a further subdivision of CD4+ T helper cell lines. The earlier definition of the TH1 and TH2 subtypes was confirmed by their differential response to interleukin (IL) 1. An additional subdivision of the TH1 subset was revealed when TH1 cell lines were costimulated with anti‐CD3 antibodies and IL2. The IL2‐induced proliferation of three of the resulting TH1 lines was blocked by anti‐CD3 antibodies. By contrast, no such block was observed in a fourth TH1 cell line. In all four lines anti‐CD3 triggering caused production of IL 2. The block of proliferation was reversed neither by antigen‐presenting cells nor by phorbol 12‐myristate 13‐acetate, a protein kinase C activator. In all TH2 cells, however, anti‐CD3 triggering led to IL4 production, but had only marginal effects on IL2‐induced cell proliferation.
Cross‐recognition of a mouse H‐2‐peptide complex by human HLA‐restricted cytotoxic T cells
Authors: Murray Ruth J. , Brooks Jill M. , Rickinson Alan B. , Rowe Martin 
Published: March 2007

AbstractEpstein‐Barr virus (EBV)‐specific human cytotoxic T lymphocyte (CTL) lines from a virus‐immune HLA‐A11+ donor CMc produced significant lysis of transfected mouse P815 target cells (H‐2d background) expressing an introduced HLA‐A11 heavy chain gene and the EBV gene encoding latent membrane protein (LMP). To identify the target epitope being recognized, HLA‐A11+ transfectants of P815/A11) were pre‐exposed to synthetic peptides corresponding to fragments of the LMP sequence and the cells then tested for lysis by CMc effectors; untransfected P815 parent cells were included in these assays as control recipients of the same peptides. Unexpectedly, we identified a peptide preparation (corresponding to LMP residues 124–137) which specifically sensitized not only P815/A11 cells but also the parental P815 cells to lysis. Four independent anti‐EBV CTL lines derived from donor CMc gave the same result and single‐cell cloning confirmed that lysis was mediated by a subset of the HLA‐A11‐restricted EBV‐specific CTL clones which dominate CMc effector populations. Two lines of evidence indicated that peptide presentation to the human CTL was occurring through H‐2Kd molecules on the surface of P815/A11 and P815 cells: (a) a monoclonal antibody reactive with H‐2Kd specifically blocked the lysis of both P815/A11 and P815 peptide‐treated targets, and (b) on an extended target cell panel, peptide‐mediated sensitization was also obtained with a second H‐2d mouse line A20.2J and with an H‐2Kd transfectant of the H‐2k line R1E. This work has therefore identified EBV‐specific HLA‐A11‐restricted human CTL which show fortuitous cross‐recognition of a synthetic peptide in the context of a mouse H‐2Kd molecule. Such potential for xenogeneic cross‐reactivity needs to be borne in mind in situations where the target specificity of human CTL is being analyzed on HLA gene‐transfected murine target lines.
Differences in specificity of “DPw2‐specific” cytotoxic T cell clones revealed with HLA‐mutant lines: Evidence that non‐DP HLA genes influence recognition by some clones
Authors: Pérez Miguel Sánchez , Orejas Rosalia Diez , Petersen Jean W. , de Mars Robert , Shaw Stephen 
Published: March 2007

AbstractSeven allospecific cytotoxic T lymphocyte (CTL) clones derived from DPw2‐specific bulk populations were characterized by three approaches to obtain a more detailed understanding of the T cell recognition of the HLA‐DPw2 molecule. All seven of the clones were DPw2 specific and indistinguishable in specificity by three approaches: (a) patterns of lysis of panels of targets from normal donors; (b) inhibition of lysis by anti‐class II monoclonal antibodies (mAb); (c) lysis of mutant lymphoblastoid B cell Lines (LCL) with isolated loss of DP2α or DP2β gene expression (as a result of selection for resistance to DPw2‐specific CTL). However, only four of the seven CTL clones (which we designate “orthodox”) lysed all mutant DPw2+ LCL tested; the other three (“heterodox”) CTL clones showed reduced or no lysis of particular LCL which expressed DPw2 but had been mutagenized and selected for loss of DR expression. Cold target blocking experiments with the mutant LCL confirmed differences in: (a) specificity among CTL clones and (b) CTL‐defined phenotype among serologically indistinguishable DR−DPw2+ mutant LCL. Differences were not explained by different levels of DP expression by the mutant LCL. Given the nature of the mutagens and mutations, it is highly improbable that point mutations in DP account for differences in recognition. These data suggest that non‐DP HLA genes influence recognition by some DP‐specific clones, potentially due to corecognition of HLA‐DRα or another non‐DP HLA product in the context of a DPw2α/β dimer.
An exact comparison between the efficiency of two‐ and three‐cell‐type clusters in mediating helper activity
Authors: Avrion Mitchison N. 
Published: March 2007

AbstractAdoptive transfer of anti‐H‐2Db‐primed B cells combined with anti‐minor histocompatibility antigen‐primed T cells enables the effect of linked and unlinked alloantigen to be compared. Over an extensive dose range the unlinked antigen proved ineffective. In a previously described, exactly comparable system for assessing the same effect on cytotoxic T cell precursors, low doses of linked antigen had proved approximately equally effective, but high doses of unlinked antigen had proved effective. This contrast supports the hypothesis that whereas T‐B collaboration is mediated by two‐cell‐type clusters, collaboration between T cells requires formation of three‐cell‐type clusters.
Mapping of the full profile of T cell allorecognition regions on HLA‐DR2β subunit
Authors: Ulrich Robert G. , Zouhair Atassi M. 
Published: March 2007

AbstractAlloreactive human T cell lines were developed by repeated in vitro restimulation with alternate allogeneic cells of similar DR2 serotype, but differing at other HLA loci. These polyclonal T cells recognized DR specificities in common with all DR2 serotypes. The allorecognition profiles of DR2β by the T cell lines were mapped by consecutive uniform‐sized overlapping peptides encompassing the entire extracellular and intracellular regions of the DRP subunit. It was found that the T cell allorecognition sites are focused around the first and third polymorphic regions of the N‐terminal domain, and interestingly, include conserved areas in the DRβ second domain as well as the intracellular segment β222–237. These findings have important implications for allorecognition. Comparison with the previous analysis of antibody‐binding regions of DR2β revealed some similarities and differences in the antibody and T cell alloresponses to this histocompatibility antigen.
Autoimmune diseases linked to abnormal K+ channel expression in double‐negative CD4−CD8− T cells
Authors: George Chandy K. , Cahalan Michael D. , Grissmer Stephan 
Published: March 2007

AbstractUsing the patch‐clamp technique in combination with fluorescence microscopy we have found an abnormality in voltage‐gated K+ channel expression in T cells that represents the first molecular marker linking three disparate autoimmune diseases in mice. CD4−CD8−Thy‐1.2+ (double‐negative or DN) lymphocytes from every known murine model for systemic lupus erythematosus, type‐1 diabetes mellitus and experimental allergic encephalomyelitis exhibit abnormally high numbers of an unusual K+ channel, termed type l compared to their phenotypic counterparts in normal mice. Other T cell subsets from these diseased mice retain their normal pattern of K+ channel expression. The unique K+ channel phenotype of DN T cells arises in parallel with the onset of autoimmunity. Although mitogen‐activated T cells and rapidly proliferating thymocytes exhibit large numbers of K+ channels, these channels are of an electrophysiologically distinct type called n. Thus, abundant expression of type l K+ channels appears to be a useful marker for DN T cells associated with autoimmunity and may provide a valuable tool for delineating the role of DN T cells in the pathogenesis of autoimmune diseases.