title: In vivo selection of a TCR Vbeta repertoire directed against an immunodominant influenza virus CTL epitope.
abstract: Little is known about the mechanisms governing TCR repertoire selection in response to foreign antigens. Here, we evaluate the molecular features of the murine C57BL/6 (B6) TCR Vbeta repertoire directed at the NP(366-374) immunodominant epitope of the influenza virus nucleoprotein. Common or 'public' beta chains are shared among individuals following either primary or secondary infection. Importantly, repertoire diversity decreases substantially after a second viral exposure due to enrichment of TCRs sharing Vbeta CDR3 loops of identical length and highly related amino acid sequences. TCRs from these secondary T cell populations possess greater overall avidity for the NP(366-374)/D(b) complex compared to those from the primary repertoire. Thus, expansion of CD8(+) T cells expressing a favored germline Vbeta gene segment in the primary response and further selection for CDR3beta loops during the secondary response, contribute to optimization of immune recognition against certain viral epitopes.
authors.affiliation: Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA, USA. weimin_zhong@dfci.harvard.edu
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhong
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000235:genetics / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D019590:Nucleocapsid Proteins; D010455:Peptides