MHC II Heterozygosity Limits T Cell Receptor Variability in CD4 T Cells
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ABSTRACT: 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 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 II alleles. Surprisingly, the TCRs in heterozygotes were less diverse that those in the sum of their MHC II homozygous relatives. Our results suggest that thymus negative selection cancels out the advantages of increased thymic positive selection in the MHC heterozygotes.
ORGANISM(S): Mus musculus
PROVIDER: GSE269649 | GEO | 2024/06/16
REPOSITORIES: GEO
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