Evolution of the antigen-specific CD8+ TCR repertoire across the life span

Evidence for clonal homogenization of the old TCR repertoire

Brian D. Rudd, Vanessa Venturi, Miles P. Davenport, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 gB498-505; 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 CDR3β 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 TCRVβ10 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.

Original languageEnglish (US)
Pages (from-to)2056-2064
Number of pages9
JournalJournal of Immunology
Volume186
Issue number4
DOIs
StatePublished - Feb 15 2011

Fingerprint

CD8 Antigens
T-Lymphocytes
Human Herpesvirus 1
Inbred C57BL Mouse
Epitopes
Glycoproteins
Vaccines
Nucleotides
Parturition
Newborn Infant
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Evolution of the antigen-specific CD8+ TCR repertoire across the life span : Evidence for clonal homogenization of the old TCR repertoire. / Rudd, Brian D.; Venturi, Vanessa; Davenport, Miles P.; Nikolich-Zugich, Janko.

In: Journal of Immunology, Vol. 186, No. 4, 15.02.2011, p. 2056-2064.

Research output: Contribution to journalArticle

@article{b5f4f4429bc14eee928e3c66267116a2,
title = "Evolution of the antigen-specific CD8+ TCR repertoire across the life span: Evidence for clonal homogenization of the old TCR repertoire",
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 gB498-505; 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 CDR3β 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 TCRVβ10 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.",
author = "Rudd, {Brian D.} and Vanessa Venturi and Davenport, {Miles P.} and Janko Nikolich-Zugich",
year = "2011",
month = "2",
day = "15",
doi = "10.4049/jimmunol.1003013",
language = "English (US)",
volume = "186",
pages = "2056--2064",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Evolution of the antigen-specific CD8+ TCR repertoire across the life span

T2 - Evidence for clonal homogenization of the old TCR repertoire

AU - Rudd, Brian D.

AU - Venturi, Vanessa

AU - Davenport, Miles P.

AU - Nikolich-Zugich, Janko

PY - 2011/2/15

Y1 - 2011/2/15

N2 - 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 gB498-505; 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 CDR3β 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 TCRVβ10 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.

AB - 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 gB498-505; 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 CDR3β 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 TCRVβ10 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.

UR - http://www.scopus.com/inward/record.url?scp=79951821255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951821255&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1003013

DO - 10.4049/jimmunol.1003013

M3 - Article

VL - 186

SP - 2056

EP - 2064

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -