T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection

George C. Wang, Pradyot Dash, Jonathan Mccullers, Peter C. Doherty, Paul G. Thomas

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8 + TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV) - specific CD8 + T cells recovered directly ex vivo. We found that CD8 + TCRαβ repertoire diversity, but not the size of the CD8 + T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8 + T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

Original languageEnglish (US)
Article number128ra42
JournalScience Translational Medicine
Volume4
Issue number128
DOIs
StatePublished - Apr 4 2012
Externally publishedYes

Fingerprint

Cytomegalovirus Infections
T-Cell Antigen Receptor
Antibodies
Cytomegalovirus
T-Lymphocytes
T-Cell Antigen Receptor Specificity
Benchmarking
Infection Control
Viral Load
Immunity
Peptides
Mutation
Mortality

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection. / Wang, George C.; Dash, Pradyot; Mccullers, Jonathan; Doherty, Peter C.; Thomas, Paul G.

In: Science Translational Medicine, Vol. 4, No. 128, 128ra42, 04.04.2012.

Research output: Contribution to journalArticle

@article{a1060a95ac7f40c9aed2adc049ef3c77,
title = "T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection",
abstract = "A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8 + TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV) - specific CD8 + T cells recovered directly ex vivo. We found that CD8 + TCRαβ repertoire diversity, but not the size of the CD8 + T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8 + T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.",
author = "Wang, {George C.} and Pradyot Dash and Jonathan Mccullers and Doherty, {Peter C.} and Thomas, {Paul G.}",
year = "2012",
month = "4",
day = "4",
doi = "10.1126/scitranslmed.3003647",
language = "English (US)",
volume = "4",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "128",

}

TY - JOUR

T1 - T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection

AU - Wang, George C.

AU - Dash, Pradyot

AU - Mccullers, Jonathan

AU - Doherty, Peter C.

AU - Thomas, Paul G.

PY - 2012/4/4

Y1 - 2012/4/4

N2 - A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8 + TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV) - specific CD8 + T cells recovered directly ex vivo. We found that CD8 + TCRαβ repertoire diversity, but not the size of the CD8 + T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8 + T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

AB - A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8 + TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV) - specific CD8 + T cells recovered directly ex vivo. We found that CD8 + TCRαβ repertoire diversity, but not the size of the CD8 + T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8 + T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

UR - http://www.scopus.com/inward/record.url?scp=84859485913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859485913&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.3003647

DO - 10.1126/scitranslmed.3003647

M3 - Article

C2 - 22491952

AN - SCOPUS:84859485913

VL - 4

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 128

M1 - 128ra42

ER -