Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope
UMass Chan AffiliationsGraduate School of Biomedical Sciences, Immunology and Microbiology Program
Department of Pathology
Document TypeJournal Article
Immunology and Infectious Disease
MetadataShow full item record
AbstractA 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.
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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40343
First author InYoung Song is a doctoral student in the Immunology and Microbiology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.