Journal article
Human skin is colonized by T cells that recognize CD1a independently of lipid
RN Cotton, TY Cheng, M Wegrecki, J Le Nours, DP Orgill, B Pomahac, SG Talbot, RA Willis, JD Altman, A de Jong, G Ogg, I Van Rhijn, J Rossjohn, RA Clark, DB Moody
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2021
DOI: 10.1172/JCI140706
Abstract
CD1a-autoreactive T cells contribute to skin disease, but the identity of immunodominant self-lipid antigens and their mode of recognition are not yet solved. In most models, MHC and CD1 proteins serve as display platforms for smaller antigens. Here, we showed that CD1a tetramers without added antigen stained large T cell pools in every subject tested, accounting for approximately 1% of skin T cells. The mechanism of tetramer binding to T cells did not require any defined antigen. Binding occurred with approximately 100 lipid ligands carried by CD1a proteins, but could be tuned upward or downward with certain natural self-lipids. TCR recognition mapped to the outer A' roof of CD1a at sites r..
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Awarded by NIHR Oxford Biomedical Research Centre
Funding Acknowledgements
We thank the NIH Tetramer Core Facility staff for biotinylated CD1 proteins and HLA-DRB1 monomer and matched HEK293T cells. J. Teague provided advice on human skin culture, and BWH Division of Plastic and Reconstructive Surgery clinical staff provided surgical discarded tissue. The work is supported by the NIH (R01 AR048632, R01 AI127654, P30 AR069625, T32 AR007530), the Wellcome Trust Collaborative Award in Science, the UK Medical Research Council, the NIHR Oxford Biomedical Research Centre, the National Health and Medical Research Council of Australia, and the Australian Research Council (ARC) (CE140100011). JLN is supported by an ARC Future Fellowship (FT160100074); JR is supported by an Australian ARC Laureate Fellowship. ADJ is supported by NIH K01 AR068475.