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Age-related appearance of a CMV-specific high-avidity CD8+ T cell clonotype which does not occur in young adults Schwanninger, Angelika; Weinberger, Birgit; Weiskopf, Daniela; Herndler-Brandstetter, Dietmar; Reitinger, Stephan; Gassner, Christoph; Schennach, Harald; Parson, Walther; Würzner, Reinhard; Grubeck-Loebenstein, Beatrix

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; CMVNLV) in different age-groups. Independent of donor age CMVNLV-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 CMVNLV-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.

Item Metadata

Title
Age-related appearance of a CMV-specific high-avidity CD8+ T cell clonotype which does not occur in young adults
Creator
Schwanninger, Angelika; Weinberger, Birgit; Weiskopf, Daniela; Herndler-Brandstetter, Dietmar; Reitinger, Stephan; Gassner, Christoph; Schennach, Harald; Parson, Walther; Würzner, Reinhard; Grubeck-Loebenstein, Beatrix
Publisher
BioMed Central
Date Issued
2008-11-12
Description
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; CMVNLV) in different age-groups. Independent of donor age CMVNLV-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 CMVNLV-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.
Genre
Article
Type
Text
Language
eng
Date Available
2016-01-13
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0223383
URI
http://hdl.handle.net/2429/56488
Affiliation
Other UBC; Non UBC
Citation
Immunity & Ageing. 2008 Nov 12;5(1):14
Publisher DOI
10.1186/1742-4933-5-14
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Schwanninger et al.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)