Short report

Age-related appearance of a CMV-specific high-avidity CD8⁺ T cell clonotype which does not occur in young adults

Angelika Schwanninger^1* , Birgit Weinberger^1* , Daniela Weiskopf¹ , Dietmar Herndler-Brandstetter¹ , Stephan Reitinger¹ , Christoph Gassner² , Harald Schennach² , Walther Parson³ , Reinhard Würzner⁴ and Beatrix Grubeck-Loebenstein¹

¹  Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria

²  Central Institute for Blood Transfusion and Division for Immunology, University Hospital, 6020 Innsbruck, Austria

³  Institute of Legal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria

⁴  Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria

author email corresponding author email* Contributed equally

Immunity & Ageing 2008, 5:14doi:10.1186/1742-4933-5-14

Published:	12 November 2008

Abstract

Old age is associated with characteristic changes of the immune system contributing to higher incidence and severity of many infectious diseases. Particularly within the T cell compartment latent infection with human Cytomegalovirus (CMV) is contributing to and accelerating immunosenescence. However, latent CMV infection and reactivation usually does not cause overt symptoms in immunocompetent elderly persons indicating immunological control of disease. Little is still known about the clonal composition of CMV-specific T cell responses in donors of different age. We therefore analyzed CD8⁺ T cells specific for an immunodominant pp65-derived nonamer-peptide (NLVPMVATV; CMV_NLV) in different age-groups. Independent of donor age CMV_NLV-specific CD8⁺ T cells preferentially use the V beta family 8. This family has monoclonal expansions in the majority of donors after stimulation of CD8⁺ T cells with the peptide. By sequencing the CDR3 region of the T cell receptor we demonstrated that CMV_NLV-specific, BV8⁺ CD8⁺ T cells share the conserved CDR3-sequence motif SANYGYT in donors of all age groups. Interestingly, a second conserved clonotype with the CDR3-sequence motif SVNEAF appears in middle-aged and elderly donors. This clonotype is absent in young individuals. The age-related clonotype SVNEAF binds to the pMHC-complex with higher avidity than the clonotype SANYGYT, which is predominant in young adults. The dominance of this high avidity clonotype may explain the lack of overt CMV-disease in old age.