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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

. 2021 ; 131 (1) : . [pub] 20210104

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22000902

Grantová podpora
R01 AI127654 NIAID NIH HHS - United States
P30 AR069625 NIAMS NIH HHS - United States
MC_UU_00008/5 Medical Research Council - United Kingdom
Department of Health - United Kingdom
T32 AR007530 NIAMS NIH HHS - United States
209222/Z/17/Z Wellcome Trust - United Kingdom
R01 AR074037 NIAMS NIH HHS - United States
R01 AR048632 NIAMS NIH HHS - United States
K01 AR068475 NIAMS NIH HHS - United States
Wellcome Trust - United Kingdom
MC_EX_MR/R022550/1 Medical Research Council - United Kingdom

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 remote from the antigen exit portal, explaining how TCRs can bind CD1a rather than carried lipids. Thus, a major antigenic target of CD1a T cell autoreactivity in vivo is CD1a itself. Based on their high frequency and prevalence among donors, we conclude that CD1a-specific, lipid-independent T cells are a normal component of the human skin T cell repertoire. Bypassing the need to select antigens and effector molecules, CD1a tetramers represent a simple method to track such CD1a-specific T cells from tissues and in any clinical disease.

Citace poskytuje Crossref.org

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$a 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 remote from the antigen exit portal, explaining how TCRs can bind CD1a rather than carried lipids. Thus, a major antigenic target of CD1a T cell autoreactivity in vivo is CD1a itself. Based on their high frequency and prevalence among donors, we conclude that CD1a-specific, lipid-independent T cells are a normal component of the human skin T cell repertoire. Bypassing the need to select antigens and effector molecules, CD1a tetramers represent a simple method to track such CD1a-specific T cells from tissues and in any clinical disease.
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