The somatically generated portion of T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

• Published in: eLife 2017-11, Vol.6
• Main Authors: Marrack, Philippa, Krovi, Sai Harsha, Silberman, Daniel, White, Janice, Kushnir, Eleanor, Nakayama, Maki, Crooks, James, Danhorn, Thomas, Leach, Sonia, Anselment, Randy, Scott-Browne, James, Gapin, Laurent, Kappler, John
• Format: Article
• Language: English
• Subjects: Alleles; Amino acids; Animals; Antigens; CDR3 alpha; Clonal selection; Complementarity-determining region 3; Genes; Histocompatibility Antigens - genetics; Histocompatibility Antigens - metabolism; Immunology; Immunology and Inflammation; Lymphocytes; Lymphocytes T; Major Histocompatibility Complex; Mice; Pathogens; Peptides; Positive selection; Protein Binding; Proteins; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; selection; Substrate Specificity; T cell receptor; T cell receptors; Thymus
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.30918

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.