title: Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+T cell epitope.
abstract: 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.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Graduate Program in Immunology and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: InYoung
authors.initials: I
authors.lastname: Song
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Gil
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Rabinarayan
authors.initials: R
authors.lastname: Mishra
authors.affiliation: School of Interdisciplinary Informatics, University of Nebraska at Omaha, Omaha, Nebraska, USA.
authors.forename: Dario
authors.initials: D
authors.lastname: Ghersi
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Graduate Program in Immunology and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Liisa K
authors.initials: LK
authors.lastname: Selin
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Graduate Program in Immunology and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.|Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Lawrence J
authors.identifier: 0000-0001-9870-8557
authors.initials: LJ
authors.lastname: Stern
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D022801:Complementarity Determining Regions / Q000737:chemistry; D018360:Crystallography, X-Ray; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000378:metabolism; D019169:Jurkat Cells; D008285:Major Histocompatibility Complex; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell