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, Nick de Vries, Dale I Godfrey, John D Altman, Wilco de Jager, Jamie Rossjohn, D Branch Moody

Research output: Contribution to journalArticleResearchpeer-review

146 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 alpha-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an alpha-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 TCRalpha 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 languageEnglish
Pages (from-to)706 - 713
Number of pages8
JournalNature Immunology
Volume14
Issue number7
DOIs
Publication statusPublished - 2013

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