A conserved human T cell population targets mycobacterial antigens presented by CD1b

Ildiko van Rhijn; Anne Kasmar; Annemieke de Jong; Stephanie Gras; Mugdha Bhati; Marieke E. Doorenspleet; Niek de Vries; Dale I. Godfrey; John D. Altman; Wilco de Jager; Jamie Rossjohn; D. Branch Moody

doi:https://doi.org/10.1038/ni.2630

A conserved human T cell population targets mycobacterial antigens presented by CD1b

Ildiko van Rhijn, Anne Kasmar, Annemieke de Jong, Stephanie Gras, Mugdha Bhati, Marieke E. Doorenspleet, Niek de Vries, Dale I. Godfrey, John D. Altman, Wilco de Jager, Jamie Rossjohn, D. Branch Moody

Research output: Contribution to journal › Article › Academic › peer-review

166 Citations (Scopus)

Abstract

Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an α-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCRα sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen

Original language	English
Pages (from-to)	706-713
Journal	Nature immunology
Volume	14
Issue number	7
DOIs	https://doi.org/10.1038/ni.2630
Publication status	Published - 2013

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https://doi.org/10.1038/ni.2630

Cite this

@article{e6908b6c8659430caa4c01c543aef12f,

title = "A conserved human T cell population targets mycobacterial antigens presented by CD1b",

abstract = "Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an α-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCRα sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen",

author = "{van Rhijn}, Ildiko and Anne Kasmar and {de Jong}, Annemieke and Stephanie Gras and Mugdha Bhati and Doorenspleet, {Marieke E.} and {de Vries}, Niek and Godfrey, {Dale I.} and Altman, {John D.} and {de Jager}, Wilco and Jamie Rossjohn and Moody, {D. Branch}",

year = "2013",

doi = "https://doi.org/10.1038/ni.2630",

language = "English",

volume = "14",

pages = "706--713",

journal = "Nature immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

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T1 - A conserved human T cell population targets mycobacterial antigens presented by CD1b

AU - van Rhijn, Ildiko

AU - Kasmar, Anne

AU - de Jong, Annemieke

AU - Gras, Stephanie

AU - Bhati, Mugdha

AU - Doorenspleet, Marieke E.

AU - de Vries, Niek

AU - Godfrey, Dale I.

AU - Altman, John D.

AU - de Jager, Wilco

AU - Rossjohn, Jamie

AU - Moody, D. Branch

PY - 2013

Y1 - 2013

N2 - Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an α-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCRα sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen

AB - Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an α-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCRα sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen

U2 - https://doi.org/10.1038/ni.2630

DO - https://doi.org/10.1038/ni.2630

M3 - Article

C2 - 23727893

SN - 1529-2908

VL - 14

SP - 706

EP - 713

JO - Nature immunology

JF - Nature immunology

IS - 7

ER -