We have previously described a mouse strain congenic for the T-cell receptor alpha chain locus (Tcra). The strain, B10.D2.C-Tcraa/Bo, carries the Tcraa haplotype of BALB/c instead of the Tcrab haplotype normally found in B10.D2. By comparing B10.D2.C-Tcraa and B10.D2 mice, we now show that the Tcra haplotype influences the frequencies of V alpha 8 epitope expression on T cells detected by the novel B21.14 monoclonal antibody (MoAb). This finding agrees well with our previous observation that Tcra haplotype influences the frequencies of expression of two other V alpha 8 epitopes, detected by the KT50 and KT65 MoAbs. The specificities of the three V alpha 8-specific MoAbs were compared by scatter diagram analysis of staining frequencies obtained in individual mice. The B21.14 and KT50 MoAbs appear to have very similar specificities; these two MoAbs stain slightly more alpha beta T cells than the KT65 MoAb. Investigations with another novel MoAb, the V alpha 2-specific B20.1, revealed that the Tcra haplotype also influences the frequency of V alpha 2 epitope expression. The effect of the Tcra haplotype on V alpha 2 epitope expression was evident not only among lymph node T cells but also among mature, cortisone-resistant thymocytes. Thus, the influence of the Tcra haplotype is imprinted already in the thymus. The most likely explanations for Tcra haplotype dependency of V alpha epitope expression are differing numbers of V alpha-gene segment subfamily members and/or allelic polymorphism. The significance of Tcra haplotype-dependent V alpha epitope expression is discussed.
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Br J Haematol
January 2025
Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Acquired aplastic anaemia (AA) is an autoimmune bone marrow failure disease resulting from a cytotoxic T-cell-mediated attack on haematopoietic stem and progenitor cells (HSPCs). Despite significant progress in understanding the T-cell repertoire alterations in AA, identifying specific pathogenic T cells in AA patients has remained elusive, primarily due to the unknown antigenic targets of the autoimmune attack. In this review, we will synthesize findings from several decades of research to critically evaluate the current knowledge on T-cell repertoires in AA.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Ji'nan 250012, China. Electronic address:
The continuing emergence of SARS-CoV-2 variants has posed a great challenge to vaccination strategies. Therefore, the development of broad-spectrum protective antibodies and universal vaccines remains urgently needed. In this study, we isolated two broadly neutralizing mAbs, nCoV-R48 and nCoV-R70, from a vaccinated person.
View Article and Find Full Text PDFNat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Division of Rheumatology, Center of Excellence for Intestinal and Immunology Research, University of Alberta, Edmonton, Alberta, Canada.
Superantigen-induced (Sag-induced) autoimmunity has been proposed as a mechanism for many human disorders, without a clear understanding of the potential triggers. In this issue of the JCI, McCarthy and colleagues used the SKG mouse model of rheumatoid arthritis to characterize the role of Sag activity in inflammatory arthritis by profiling arthritogenic naive CD4+ T cells. Within the diseased joints, they found a marked enrichment of T cell receptor-variable β (TCR-Vβ) subsets that were reactive to the endogenously encoded mouse mammary tumor virus (MMTV) Sag.
View Article and Find Full Text PDFNPJ Vaccines
January 2025
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Dysentery caused by Shigella species remains a major health threat to children in low- and middle-income countries. There is no vaccine available. The most advanced candidates, i.
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