Broad TCR Repertoire And Diverse Structural Solutions To Recognition Of An Immunodominant CD8 T Cell Epitope

A keystone of antiviral immunity is CD8 T-cell recognition of viral peptides bound to MHC-I proteins. The recognition mode of individual T cell receptors (TCRs) has been studied in some detail, but how TCR variation functions in providing a robust response to viral antigen is unclear. The influenza M1 epitope is an immunodominant target of CD8 T cells helping to control influenza in HLA-A2+ individuals. Here, we show that many distinct TCRs are used by CD8 T cells to recognize HLA-A2/M1, encoding different structural solutions to the problem of specifically recognizing a relatively featureless peptide antigen. The vast majority of responding TCRs target small clefts between peptide and MHC. These broad repertoires lead to plasticity in antigen recognition and protection against T cell clonal loss and viral escape.