Journal article
A conserved human T cell population targets mycobacterial antigens presented by CD1b
I Van Rhijn, A Kasmar, A De Jong, S Gras, M Bhati, ME Doorenspleet, N De Vries, DI Godfrey, JD Altman, W De Jager, J Rossjohn, DB Moody
Nature Immunology | Published : 2013
DOI: 10.1038/ni.2630
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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Grants
Awarded by National Institute of Allergy and Infectious 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.).