| Autor: |
Brown, Alexander J., White, Janice, Shaw, Laura, Gross, Jimmy, Slabodkin, Andrei, Kushner, Ella, Greiff, Victor, Matsuda, Jennifer, Gapin, Laurent, Scott-Browne, James, Kappler, John, Marrack, Philippa |
| Předmět: |
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| Zdroj: |
Science Immunology; Jul2024, Vol. 9 Issue 97, p1-16, 16p |
| 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. Editor's summary: T cells undergo positive and negative selection in the thymus through T cell receptor (TCR) recognition of peptides presented on major histocompatibility (MHC) proteins. Although the genes encoding MHC proteins are among the most polymorphic, most vertebrates individually express relatively few MHC alleles. How the number of MHC alleles expressed affects thymic selection and the TCR repertoire on an individual level remains unclear. Using mice expressing different MHC loci on the same background, Brown et al. compared the TCR repertoires of naïve CD4 T cells from MHC homozygous and heterozygous mice. MHC heterozygotes expressed a less diverse TCR repertoire than expected compared with their MHC homozygous relatives, likely because of increased rates of negative selection. These findings suggest that the number of MHC alleles expressed in an individual animal has been evolutionarily optimized to minimize "holes" in the TCR repertoire. —Claire Olingy [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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