bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of free thiol group(s) on autoantibody-defined epitope of proliferating cell nuclear antigen.
Authors: Tsai W M , Roos G , Hugli T E , Tan E M 
Published: January 2023

Abstract
Proliferating cell nuclear Ag (PCNA) is an intranuclear protein involved in DNA replication directed by DNA polymerase delta and is the target Ag of autoantibodies in some patients with SLE. There is evidence that the epitope on PCNA recognized by human autoantibodies is conformation-dependent and is not a continuous peptide sequence. Thimerosal, a mercury-containing sulfhydryl blocking compound, markedly reduced or abolished the reactivity of this autoantibody-defined PCNA epitope. The thimerosal effect was observed in various Ag-detecting systems including indirect immunofluorescence, immunodiffusion, immunoprecipitation, and flow cytometry. The mechanism of the thimerosal effect appeared to be mediated through free but not readily accessible sulfhydryl group or groups. The sulfhydryl-modification by thimerosal could be reversed by competition with thiol-containing compounds. Experimentally induced mAb to PCNA generated by immunization with purified PCNA have been shown to recognize epitopes that are continuous peptide sequences and these epitopes were not affected by thimerosal. It has been shown that the human autoantibody-defined epitope is related to the function of PCNA because autoantibodies are able to inhibit DNA polymerase delta directed DNA replication, whereas experimentally induced antibodies are not. These studies show that certain sulfhydryl groups in PCNA have a role in determining the antigenicity of the epitope recognized by autoantibody and raise the possibility that certain sulfhydryl groups might also be associated with its function.
Carbon Dioxide Studies
Authors: Valley George , McAlpine James G. 
Published: January 2023

Abstract
The various methods which have been employed for the preservation of guinea pig serum alexin have relied on the efficacy of low temperature, either alone or in conjunction with additional chemical treatment.
The results of Stern (1908) with “Frigo” complement, and those of Morgenroth (1910), Noguchi and Bronfenbrenner (1911), Penecke (1913), Browning and Mackie (1913–1914), Weston (1915), Moledezky (1918), Bigger (1919), Ruediger (1919, 1922), Rivers (1927), Norton, Barfield and Falk (1927) furnish abundant evidence concerning the merits and demerits of low temperature preservation.
A combination of low temperature and salting has been advocated by Austin (1914), Thompson (1916), Ottenberg (1917), Neill (1918), and Kolmer, Matsunami and Trist (1919). The use of sodium chloride in amounts varying from 4 to 37 per cent has been suggested. Rhamy (1917) employed sodium acetate, while Ruediger (1919) suggested the use of glycerol.
Aside from the above-mentioned methods, drying has been advocated by Noguchi (1910), but considered impractical since the dried alexin on filter-paper lost its potency quite rapidly.
Ophthalmic Test for Horse Serum Sensitivity Contrasted with the Intradermal
Authors: Spicer Sophie 
Published: January 2023

Abstract
Before injecting antitoxin, it is important to ascertain the sensitivity of the patient to horse serum, so that any possible reaction may be prepared for and alleviated. It is desirable that the test given be both prompt and certain in its action.
To determine the relative value of the ophthalmic as compared with the intradermal sensitivity test, a series of 353 patients was tested with normal horse serum, at the Willard Parker Hospital, New York City. The series consisted of 247 diphtheria and 106 scarlet fever patients. Both tests were performed on each patient twenty minutes before administration of antitoxin, and readings were taken ten to twenty minutes and twenty-four hours after test.
Normal horse serum was used in different dilutions, namely: 1:10, 1:2, 1:1 with normal saline solution serving as the diluent, and finally straight, undiluted horse serum was employed.
Parenteral Denaturization of Foreign Proteins
Authors: Manwaring W. H. , Marino H. D. , Azevedo J. L. , Torbert H. C. 
Published: January 2023

Summary and Conclusions
The rate of parenteral denaturization of horse proteins in horse serum immune dogs, therefore, is distinctly slower than the rate in normal dogs. There is not the rapid denaturization previously observed in hypersensitive dogs, all tests with hypersensitive donors being negative after the eighteenth hour (1). Nor is there the still more rapid denaturization one would predict from the unitarian conception of the relation of anaphylaxis to immunity. The biochemical properties or relationships responsible for rapid protein denaturization in hypersensitive dogs are apparently wholly absent or inoperative in immune dogs.
This finding is consistent with our previous conclusion of the non-identity of specific antibodies in hypersensitive and immune dogs (3).
Studies in Anaphylaxis
Authors: Van De Carr F. R. , Lyons WM. R. , Williams O. B. 
Published: January 2023

Abstract
Recent investigations on the inhibition of anaphylactic shock by use of a blood anti-coagulant indicate a close relationship between the gross symptoms of shock and changes in the dispersion of the blood colloids. Kyes and Strauser (1), by rendering the blood incoagulable with heparin, have prevented the symptoms of anaphylaxis in sensitized pigeons. In confirmatory papers (2) (3), we have reported observations which indicate that no symptoms of anaphylaxis may be recorded in the majority of cases, in guinea pigs hypersensitive to horse serum, provided the clotting time of the blood is changed with heparin. There were, however, some instances in which the animals reacted typically to the critical dose of antigen, although the blood had previously been rendered incoagulable.
It is the purpose of this paper to offer a possible explanation for these observations, and to present certain findings that tend to support the theory on the physico-chemical nature of anaphylaxis, in particular the nature of the symptoms observed in guinea pigs.
Subsets of activated CD4 T lymphocytes refractory for secretion of IL-2 are distinguished by expression of Ly-6A/E in BALB/c mice.
Authors: Codias E K , Malek T R 
Published: January 2023

Abstract
Ly-6A/E, a cell surface glycosylphosphatidylinositol-anchored protein that modulates T cell activation, is expressed on developing and mature T cells and is tightly regulated in a haplotype- and subset-specific manner. We examined whether Ly-6A/E(low)CD4+ and Ly-6A/E(high)CD4+ T cells comprised functional subsets. Peripheral CD4+ T cells were primed in vitro with Con A in the presence or absence of IL-4 or IFN-gamma, sorted for Ly-6A/E expression, and restimulated to induce lymphokine production. Regardless of priming conditions, IL-2 production by Ly-6A/E(high)CD4+ effector T cells was markedly reduced (mean = 83%) compared to the Ly-6A/E(low)CD4+ subset. The Ly-6A/E(high)CD4+ subset also produced less IFN-gamma than Ly-6A/E(low)CD4+ cells and little IL-4 when primed without exogenous IL-4. In contrast, Ly-6A/E(high)CD4+ cells primed with exogenous IL-4 produced ample IL-4 and IFN-gamma. Interestingly, the difference in IL-2 production between Ly-6A/E(low) and Ly-6A/E(high)CD4+ subsets was not due to a failure of the Ly-6A/E(low)CD4+ cells to become primed because substantially greater amounts of IL-2 and IL-4 were produced by the Con A-pretreated Ly-6A/E(low)CD4+ subset in comparison to unprimed Ly-6A/E(low)CD4+ cells. Taken together these data suggest Ly-6A/E marks a subset of CD4+ effector T cells that differs from Ly-6A/E(low)CD4+ cells by a greatly reduced capacity to produce IL-2 but not IL-4.
Naturally processed cytokine-derived peptide bound to HLA-class II molecules.
Authors: Harris P E , Maffei A , Liu Z , Colovai I , Reed E F , Inghirami G , Suciu-Foca N 
Published: January 2023

Abstract
Sequence analysis of HLA-class II (HLA-DR beta 1-1502 and 1104)-bound self-peptides from a transformed B cell line was performed. The sequences of naturally processed self-peptides bound to HLA-DR2 and DR5 were compared with protein and nucleic acid data bases for homology to known precursor proteins. Of the matches to known precursors, one peptide showed 100% homology to the third framework and CDR3 regions of Ig VH expressed by the line. Another peptide matched 100% to the human equivalent of macrophage inflammatory protein (MIP). A synthetic peptide corresponding to the naturally processed form of MIP (KPGVIFLTKRSRQV) was shown to inhibit Ag-specific HLA-DR beta 1*1104-restricted T cell proliferation. This indicates that the MIP peptide binds to HLA-DR beta 1*1104. The MIP peptide belongs to a set of peptides that showed uniform NH2-terminal processing. In this set, proline always occurred as the second residue followed by a basic lysine or arginine in position nine. This suggests that final NH2-terminal processing of peptides precedes their binding to MHC molecules. A distinct, second set of peptides showed ragged NH2-terminii, as has been reported for other naturally processed MHC-class II-bound self-peptides.
Elevation of intracellular cAMP in human T lymphocytes by an anti-CD44 mAb.
Authors: Rothman B L , Kennure N , Kelley K A , Katz M , Aune T M 
Published: January 2023

Abstract
Regulation of lymphocyte responses to activation of the CD3/TCR complex by other cell surface proteins expressed on lymphocytes is a well established phenomenon. CD44 is an example of such a cell surface protein. Anti-CD44 mAb have been identified which either stimulate or inhibit lymphocyte function. Certain anti-CD44 mAb augment proliferation and IL-2 production by T cells stimulated through the CD2 or CD3/TCR pathways. An anti-CD44 mAb with opposing properties has also been identified. This mAb inhibits activation of human T cells by preventing the rise in [Ca2+]i stimulated by OKT3. The purpose of experiments reported here was to further characterize this phenomenon. The results show that the anti-CD44 mAb, 212.3, does not inhibit inositol phosphate turnover stimulated by OKT3 but does inhibit elevation of intracellular [Ca2+]i in these same cells. Addition of 212.3 to purified human T cells results in a rapid increase in intracellular levels of cAMP. Elevation of cAMP by 212.3 is time- and concentration-dependent. Activation of adenylate cyclase by forskolin also results in elevation of intracellular cAMP and inhibition of the increase in [Ca2+]i stimulated by OKT3. Taken together, these data suggest that CD44 may be positively coupled to adenylate cyclase and that activation of adenylate cyclase by the anti-CD44 mAb, 212.3, may mediate the inhibition of the OKT3-stimulated elevation of [Ca2+]i.
Analysis of T cell receptors specific for recognition of class IB antigens.
Authors: Lowen L C , Aldrich C J , Forman J 
Published: January 2023

Abstract
T cells that recognize a peptide presented by a self-class IA molecule generally use a restricted repertoire of V beta and V alpha receptors. In contrast, alloreactive T cells, which recognize alloantigens that present a wide array of peptides, use a diverse repertoire, particularly in the CDR3 loop. Because the T cell repertoire directed against class IB alloantigens is not known, we examined V-D-J sequences in V beta chains specific for Qa-1 and similar sequences in both V beta and V alpha chains specific for Qa-2. We observed that 14 Qa-1-specific clones use a limited number of V beta segments and 8 of 14 express V beta 8.2 and have a conservation of charged residues in the CDR3 loop, particularly between residues 99 and 101. Thirteen of the 14 clones rearrange to the second J beta cluster and use within this cluster is restricted. Alloreactive anti-Qa-1 T cells can be assigned into three different specificity groups based on a Qa-1 modifying gene, Qdm, as well as Qa-1 epitope expression on Tap-2-deficient RMA-S cells. Receptors from members of each specificity group are more similar in their CDR3 loop to each other than members of the other groups. These data lend support to the Qa-1 class IB Ag presenting a limited number of peptides to T cells or in some manner limiting the development of a diverse alpha beta T cell repertoire. The alpha- and beta-chains from nine alloreactive anti-Qa-2 clones were analyzed. V beta use was limited to use of V beta 7 or a member of the V beta 8 family. Rearrangements were solely to the second J beta cluster. The use of V alpha and J alpha segments were diverse. Although conserved residues or motifs were observed in the CDR3 regions of both the beta- and alpha-chains, the extent of conservation was less than that for anti-Qa-1 receptors. Anti-Qa-2 T cells can be divided into two specificities, Q6 and Q7. No common features were apparent between these groups.
Selection for amino acid sequence and J beta element usage in the beta chain of DBA/2V beta b- and DBA/2V beta a-derived myoglobin-specific T cell clones.
Authors: Ruberti G , Paragas V , Kim D , Fathman C G 
Published: January 2023

Abstract
Previous experiments in our laboratory have demonstrated that there is a marked restriction on the TCR beta-chain usage in DBA/2 mice in response to the sperm whale myoglobin (SpWMb) determinant 110-121, predominated by the use of the V beta 8.2 gene element. We analyzed the response of mice that had been genetically depleted of V beta 8+ T cells by generating a DBA/2 line that carries the V beta a TCR haplotype. Despite the very limited TCR repertoire expressed by DBA/2V beta a mice, they made an excellent response after immunization with the SpWMb 110-121 peptide. Data presented in this manuscript demonstrate that there is an equally restricted TCR V beta-chain utilization in the T-cell response to the determinant SpWMb 110-121 in DBA/2V beta a mice. Unexpectedly, there was a shift of MHC restriction of this determinant to T cells in the V beta a strain when compared with the V beta b strain of DBA/2 mice. We had previously demonstrated that DBA/2 mice utilized both the hybrid E alpha dA beta d MHC molecule as well as the conventional A alpha dA beta d molecule as presenting elements in response to SpWMb 110-121. Data presented in this manuscript demonstrate that the T-cell response in DBA/2V beta a mice is entirely restricted by the A alpha dA beta d MHC class II molecule. By analyzing a panel of SpWMb 110-121-specific T-cell clones from DBA/2V beta a mice, we were able to study the TCR repertoire expressed on T cells from mice that lack the V beta 8.2 gene. The V beta usage by the panel of clones analyzed was remarkably homogeneous. Thirteen of the 17 clones analyzed used the V beta 1 gene segment. Perhaps more striking was the junctional region nucleotide and amino acid sequences that were shared among these clones and that were similar to the V beta 8.2 clones analyzed previously. All clones assayed used the J beta 2.6 element, as did the great majority of the V beta 8.2 clones analyzed from DBA/2 (and B10.D2) V beta b mice. Importantly, in each strain of mice, irrespective of the V beta utilized, each TCR appeared to have selected an acidic amino acid in the beta-chain at position 100.(ABSTRACT TRUNCATED AT 400 WORDS)
Implication of HLA-DR residues at positions 67, 71, and 86 in interaction between HLA-DR11 and peptide HA306-320.
Authors: Zeliszewski D , Golvano J J , Gaudebout P , Dorval I , Freidel C , Gebuhrer L , Betuel H , Borras-Cuesta F , Sterkers G 
Published: January 2023

Abstract
To get further insight into the role of three polymorphic DR residues located in one alpha-helix of the HLA-DR binding groove, we studied how natural substitutions at positions 67, 71, and 86 on DR11 molecules influence MHC binding and/or T cell recognition of peptide HA306-320 and of monosubstituted peptide analogues. Our results show that: 1) Reactivities of all HA306-320-specific T cell clones tested are decreased by DR substitution at position 86 and can even be lowered by additional substitutions at position 71, and at positions 71 plus 67, indicating that these three residues are functionally important. 2) The functional effects of substitutions at positions 67, 71, and/or 86 cannot be explained by a decreased affinity of HA306-320 for the substituted DR11 molecules, as determined in binding assays. 3) More likely, they are explained by modifications of the conformation, orientation, or location of the peptide once bound in the HLA groove, because each individual DR substitution at positions 86, 71, and 67 differentially affects the binding ability of the same panel of 50 monosubstituted analogues. 4) This interpretation is reinforced by the identification of a small set of monosubstituted analogues that can compensate the functional effects of DR substitutions at positions 86, 86 plus 71, or 86 plus 71 plus 67, and thus restore T cell reactivities. All together these results strongly suggest that residues 67, 71, and 86 play a key role in interactions with HA306-320, probably by modifying the way the peptide is bound within the binding groove of HLA-DR11. Using the same DR11.1-restricted clones, we identified putative T cell and DR contact residues of HA306-320 by comparing DR binding and T cell-activating capacity of the peptide analogues. This analysis suggests that: 1) Residues 310, 311, 312, 313, and 316 are putative TCR contacts. 2) Peptide HA306-320 anchors to DR11.1 molecules mainly via residue Y-309, possibly at the vicinity of DR residue 86, whereas peptide residues 315 and 317 constitute minor aggregotopes that would be at the vicinity of DR residues 71 and/or 67. 3) Finally, residues 308, 310, and 314 might also be on the MHC side of the DR-peptide-TCR complex.
Direct evidence that interferon-beta mediates enhanced HLA-class I expression in measles virus-infected cells.
Authors: Dhib-Jalbut S S , Cowan E P 
Published: January 2023

Abstract
Viral infection results in enhancement of HLA-class I expression in a number of cell types, including glial cells, which normally do not express these molecules. This enhancement may occur through a direct interaction between a viral component and the HLA-class I gene or indirectly through virus-induced soluble factors produced by infected cells. These include cytokines such as IFN-gamma, IFN-alpha/beta, and TNF-alpha, known to enhance class I expression. Measles virus (MV) infection of a human glioma cell line (U-105 MG) and of primary human umbilical vein endothelial cells enhances the expression of HLA-class I molecules on these cells. The enhancement of HLA-class I is dependent on infectious virus, as antibody-neutralized MV has no effect on class I expression. In this study, we demonstrate the presence of an HLA-class I-enhancing factor in supernatants from MV-infected cells. The supernatant class I-enhancing factor is not IFN-gamma, IFN-alpha, or TNF-alpha because MV-infected cells did not produce measurable levels of these cytokines as detected by immunoassay or polymerase chain reaction. In contrast, IFN-beta is produced by the infected cells and the supernatant class I-enhancing factor could be entirely neutralized by antibodies to IFN-beta, but not antibodies to IFN-alpha, TNF-alpha, or non-immune sera. Furthermore, preincubation of cells with neutralizing antibodies to IFN-beta prior to infection blocked MV enhancement of HLA-class I completely in the U-105 MG cells and by as much as 74% in the umbilical vein endothelial cells. The results of these experiments provide direct evidence that enhanced HLA-class I expression in MV-infected cells is mediated primarily by IFN-beta.
CD2-deficient mice generate virus-specific cytotoxic T lymphocytes upon infection with lymphocytic choriomeningitis virus.
Authors: Evans C F , Rall G F , Killeen N , Littman D , Oldstone M B 
Published: January 2023

Abstract
The major host response to many viral infections is the generation of virus-specific CTL. Many protein molecules on the surfaces of both CTL and target cells interact to mediate adhesion of the cells and generate signals that lead to T cell activation and proliferation of virus-specific CTL that then mediate lysis of infected cells. One such protein, CD2, has been shown to increase the binding affinity of CTL to infected cells, and, in addition, enhance CTL activation signals. To determine whether virus-specific CTL could be generated in the absence of CD2, mice lacking a functional CD2 gene were infected with lymphocytic choriomeningitis virus (LCMV), and the responses to the virus were monitored. CD2-deficient mice infected intracerebrally with LCMV died as a consequence of CTL-mediated choriomeningitis, similar to control littermates. Additionally, CD2-deficient mice inoculated i.p. with LCMV cleared the infection by 2 wk postinfection, as did control mice. Viral clearance in these mice was shown to be due to the generation of a vigorous virus-specific MHC-restricted CTL response. Finally, to determine whether CD2 is essential for the generation of memory CTL, we examined the ability of CD2-deficient mice to generate memory CTL to LCMV and found normal memory CTL responses. Our results indicate that CD2 is not required for the generation of an LCMV-specific CTL response in vivo, nor is CD2 required for the maintenance or activation of memory CTL.
Conglutinin acts as an opsonin for influenza A viruses.
Authors: Hartshorn K L , Sastry K , Brown D , White M R , Okarma T B , Lee Y M , Tauber A I 
Published: January 2023

Abstract
Since the 1940's, non-Ig inhibitors of influenza A virus (IAV) hemagglutination activity and infectivity have been recognized in mammalian sera. Recently, the heat labile (beta) inhibitor of this type was identified by indirect methods as the lectin, conglutinin. In support of this hypothesis, we found that purified conglutinin strongly inhibited hemagglutination activity and infectivity of IAV. By using IAV strains with specific variations in glycosylation of the hemagglutinin molecule, we showed these effects to be mediated by binding of conglutinin to high mannose carbohydrate attachments on the viral hemagglutinin. Through the same mechanism conglutinin caused aggregation of IAV particles. Human neutrophils produce hydrogen peroxide upon exposure to IAV. Also, after a brief period of exposure to IAV, neutrophils exhibit depressed responsiveness (deactivation) upon exposure to other stimuli (e.g., chemotactic peptides). These phenomena may be related to the in vivo inflammatory response during IAV infection, and to the propensity of IAV-infected subjects to suffer bacterial superinfection. Pre-incubation of IAV with conglutinin markedly potentiated human neutrophil hydrogen peroxide production in response to the virus. This effect correlated with the ability of conglutinin to aggregate the virus. IAV treated with conglutinin also caused significantly less neutrophil deactivation than did the unopsonized virus. These enhancements of neutrophil respiratory burst responses by conglutinin were again mediated by binding of the lectin to viral carbohydrates. The mammalian C-type lectin family includes conglutinin, mannose-binding protein, and surfactant proteins A and D. These lectins may be important constituents of the initial host response to IAV, by inhibiting IAV infectivity directly, causing viral aggregation, and acting as opsonins to enhance phagocyte responses to the virus.