Epitopes described in "Evolution of the antigen-specific CD8+ TCR repertoire across the life span: evidence for clonal homogenization of the old TCR repertoire."

Article Authors:Brian D Rudd; Vanessa Venturi; Miles P Davenport; Janko Nikolich-Zugich
Article Title:Evolution of the antigen-specific CD8+ TCR repertoire across the life span: evidence for clonal homogenization of the old TCR repertoire.
Reference Detail
Reference ID:1021529
Abstract:Defects in T cell responses against pathogens and reduced diversity of TCRs have been described at both extremes of the life span. Yet, we still lack information on how Ag-specific T cell populations are maintained and/or altered from birth to old age. In this study, for the first time to our knowledge, we provide insight into Ag-specific TCR repertoire changes over the life span at the single-cell level. We have examined the TCR diversity of the primary CD8(+) T cell response to the immunodominant HSV-1 epitope HSV glycoprotein B 495-502 (HSV gB(498-505); SSIEFARL) (gB-8p) in neonatal, adult, and old C57BL/6 mice. The global distinctive features of the gB-8p-specific TCR repertoire were preserved in mice of different ages. However, both old and especially neonatal mice exhibited significant decreases in TCR diversity compared with that of adult mice. Still, although the neonatal Ag-specific repertoire comprised expectedly shorter germline-biased CDR3 lengths, the repertoire was surprisingly complex, and only a minority of responding cells lacked random nucleotide additions. Changes with aging included increased use of the already dominant TCRV10 family, a trend for lower content of the TCR containing the germline WG motif in the CDR3, and a remarkable sharing of one dominant clonotype between individual old mice, implying operation of selective mechanisms. Implications for the rational design of vaccines for neonates and the elderly are discussed.
Reference Type:Literature
PubMed ID:21248263
Journal:J Immunol
Journal Volume:186
Article Pages:2056-64
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;Immunodominant Epitopes;Immunoglobulin Variable Region;Peptide Fragments;Receptors, Antigen, T-Cell, alpha-beta;Viral Envelope Proteins;glycoprotein B, Simplexvirus
Article MeSH List:Animals; Animals, Newborn; CD8-Positive T-Lymphocytes(immunology; metabolism; virology); Cell Aging(genetics; immunology); Clone Cells; Epitopes, T-Lymphocyte(genetics; immunology); Evolution, Molecular; Herpesvirus 1, Human(immunology); Immunodominant Epitopes(genetics; immunology); Immunoglobulin Variable Region(biosynthesis; genetics); Longevity(genetics; immunology); Male; Mice; Mice, Inbred C57BL; Peptide Fragments(biosynthesis; genetics); Receptors, Antigen, T-Cell, alpha-beta(biosynthesis; genetics; metabolism); Vaccinia virus(genetics; immunology); Viral Envelope Proteins(biosynthesis)
Curation Last Updated:2015-07-30 20:39:02