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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 na\u00efve 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.<\/jats:p>","DOI":"10.1126\/sciimmunol.ado5295","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T17:58:14Z","timestamp":1720807094000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["MHC heterozygosity limits T cell receptor variability in CD4 T cells"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9638-7400","authenticated-orcid":true,"given":"Alexander J.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Immunology and Genomic Medicine, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA."},{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, 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