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 I, Gil A, Mishra R, Ghersi D, Selin LK, Stern LJ. (2017). Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope. Open Access Publications by UMass Chan Authors. https://doi.org/10.1038/nsmb.3383. Retrieved from https://escholarship.umassmed.edu/oapubs/3142