MHC heterozygosity limits T cell receptor variability in CD4 T cells.

Autor: Brown AJ; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA., White J; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA., Shaw L; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA., Gross J; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA., Slabodkin A; Department of Immunology, University of Oslo and Oslo University Hospital, Postboks 4950 Nydalen OUS HF Rikshospitalet, 0424 Oslo, Norway., Kushner E; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA., Greiff V; Department of Immunology, University of Oslo and Oslo University Hospital, Postboks 4950 Nydalen OUS HF Rikshospitalet, 0424 Oslo, Norway., Matsuda J; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA., Gapin L; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA., Scott-Browne J; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA., Kappler J; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA.; Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, 1775 Aurora Ct, Aurora, CO 80045, USA., Marrack P; Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA.; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Jul 12; Vol. 9 (97), pp. eado5295. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1126/sciimmunol.ado5295
Abstrakt: αβ T cell receptor (TCR) V(D)J genes code for billions of TCR combinations. However, only some appear on peripheral T cells in any individual because, to mature, thymocytes must react with low affinity but not high affinity with thymus expressed major histocompatibility (MHC)/peptides. MHC proteins are very polymorphic. Different alleles bind different peptides. Therefore, any individual might express many different MHC alleles to ensure that some peptides from an invader are bound to MHC and activate T cells. However, most individuals express limited numbers of MHC alleles. To explore this, we compared the TCR repertoires of naïve CD4 T cells in mice expressing one or two MHC alleles. Unexpectedly, the TCRs in heterozygotes were less diverse that those in the sum of their MHC homozygous relatives. Our results suggest that thymus negative selection cancels out the advantages of increased thymic positive selection in the MHC heterozygotes.
Databáze: MEDLINE
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