Epitopes described in "Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA."

Article Authors:Stephen J Griffiths; Natalie E Riddell; Joanne Masters; Valentina Libri; Sian M Henson; Anne Wertheimer; Diana Wallace; Stuart Sims; Laura Rivino; Anis Larbi; David M Kemeny; Janko Nikolich-Zugich; Florian Kern; Paul Klenerman; Vince C Emery; Arne N Akbar
Article Title:Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.
Reference Detail
Reference ID:1025879
Abstract:The mechanisms regulating memory CD8(+) T cell function and homeostasis during aging are unclear. CD8(+) effector memory T cells that re-express CD45RA increase considerably in older humans and both aging and persistent CMV infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated in the CD8 binding domain to identify CMV-specific CD8(+) T cells with high Ag-binding avidity. In individuals who were HLA-A*0201, CD8(+) T cells that expressed CD45RA and were specific for the pp65 protein (NLVPMVATV epitope) had lower avidity than those that expressed CD45RO and demonstrated decreased cytokine secretion and cytolytic potential after specific activation. Furthermore, low avidity NLVPMVATV-specific CD8(+) T cells were significantly increased in older individuals. The stimulation of blood leukocytes with CMV lysate induced high levels of IFN- that in turn induced IL-15 production. Moreover, the addition of IL-15 to CD45RA(-)CD45RO(+) CMV-specific CD8(+) T cells induced CD45RA expression while Ag activated cells remained CD45RO(+). This raises the possibility that non-specific cytokine-driven accumulation of CMV-specific CD8(+)CD45RA(+) T cells with lower Ag-binding avidity may exacerbate the effects of viral reactivation on skewing the T cell repertoire in CMV-infected individuals during aging.
Affiliations:Division of Infection and Immunity, University College London, London WC1E 6BT, United Kingdom.
Reference Type:Literature
PubMed ID:23636061
Journal:J Immunol
Journal Volume:190
Article Pages:5363-72
Journal ISSN:0022-1767
Article Chemical List:Antigens;HLA-A*02:01 antigen;HLA-A2 Antigen;Interferon-alpha;Interleukin-15;Phosphoproteins;Viral Matrix Proteins;cytomegalovirus matrix protein 65kDa;Antigens, CD45
Article MeSH List:Age Factors; Antibody Affinity(immunology); Antigens(immunology; metabolism); Antigens, CD45(metabolism); CD8-Positive T-Lymphocytes(immunology; metabolism); Cytomegalovirus(immunology); Cytomegalovirus Infections(immunology); Dendritic Cells(immunology; metabolism); HLA-A2 Antigen(immunology; metabolism); Humans; Immunophenotyping; Interferon-alpha(biosynthesis); Interleukin-15(immunology; metabolism); Lymphocyte Activation(immunology); Monocytes(immunology; metabolism); Phosphoproteins(immunology); Viral Matrix Proteins(immunology)
Curation Last Updated:2015-06-07 20:26:06