Journal article

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

NATURE IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 2013

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 ant..

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University of Melbourne Researchers

Grants

Awarded by US National Institute of Allergy and Infectious Diseases


Awarded by Nederlands Wetenschappelijk Onderzoek (Meervoud)


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

We thank the Tetramer Core Facility of the US National Institutes of Health for CD1b protein; M. Turner, C. Seshadri and the Shattuck Hospital for clinical collaboration; L. Tan for technical help; and the beamline staff at the Australian synchrotron for assistance with data collection. Supported by the US National Institute of Allergy and Infectious Diseases (AI04393, AR048632 to D. B. M., and K08 AI089858 to A. K.) the Burroughs Wellcome Fund, Nederlands Wetenschappelijk Onderzoek (Meervoud 836.08.001 to I. V. R.), the National Health and Medical Research Council (D. I. G. and J.R.) and the Australian Research Council (S.G.).