Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope
Department of Pathology; Graduate School of Biomedical Sciences, Immunology and Microbiology Program
Biochemistry | Immunology and Infectious Disease | Immunopathology | Molecular Biology | Structural Biology
A keystone of antiviral immunity is CD8+ T cell recognition of viral peptides bound to MHC-I proteins. The recognition modes of individual T cell receptors (TCRs) have been studied in some detail, but the role of TCR variation in providing a robust response to viral antigens is unclear. The influenza M1 epitope is an immunodominant target of CD8+ T cells that help to control influenza in HLA-A2+ individuals. Here we show that CD8+ T cells use many distinct TCRs to recognize HLA-A2-M1, which enables the use of different structural solutions to the problem of specifically recognizing a relatively featureless peptide antigen. The vast majority of responding TCRs target a small cleft between HLA-A2 and the bound M1 peptide. These broad repertoires lead to plasticity in antigen recognition and protection against T cell clonal loss and viral escape.
DOI of Published Version
Nat Struct Mol Biol. 2017 Apr;24(4):395-406. doi: 10.1038/nsmb.3383. Epub 2017 Feb 27. Link to article on publisher's site
Nature structural and molecular biology
Song, InYoung; Gil, Anna; Mishra, Rabinarayan; Ghersi, Dario; Selin, Liisa K.; and Stern, Lawrence J., "Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope" (2017). Open Access Articles. 3142.