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Human ?? T cells recognize CD1b by two distinct mechanisms.


ABSTRACT: ?? T cells form an abundant part of the human cellular immune system, where they respond to tissue damage, infection, and cancer. The spectrum of known molecular targets recognized by V?1-expressing ?? T cells is becoming increasingly diverse. Here we describe human ?? T cells that recognize CD1b, a lipid antigen-presenting molecule, which is inducibly expressed on monocytes and dendritic cells. Using CD1b tetramers to study multiple donors, we found that many CD1b-specific ?? T cells use V?1. Despite their common use of V?1, three CD1b-specific ?? T cell receptors (TCRs) showed clear differences in the surface of CD1b recognized, the requirement for lipid antigens, and corecognition of butryophilin-like proteins. Several V? segments were present among the CD1b-specific TCRs, but chain swap experiments demonstrated that CD1b specificity was mediated by the V?1 chain. One of the CD1b-specific V?1+ TCRs paired with V?4 and shows dual reactivity to CD1b and butyrophilin-like proteins. ?? TCRs typically recognize the peptide display platform of MHC proteins. In contrast, our results demonstrate the use of rearranged receptors to mediate diverse modes of recognition across the surface of CD1b in ways that do and do not require carried lipids.

SUBMITTER: Reijneveld JF 

PROVIDER: S-EPMC7502712 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Human γδ T cells recognize CD1b by two distinct mechanisms.

Reijneveld Josephine F JF   Ocampo Tonatiuh A TA   Shahine Adam A   Gully Benjamin S BS   Vantourout Pierre P   Hayday Adrian C AC   Rossjohn Jamie J   Moody D Branch DB   Van Rhijn Ildiko I  

Proceedings of the National Academy of Sciences of the United States of America 20200831 37


γδ T cells form an abundant part of the human cellular immune system, where they respond to tissue damage, infection, and cancer. The spectrum of known molecular targets recognized by Vδ1-expressing γδ T cells is becoming increasingly diverse. Here we describe human γδ T cells that recognize CD1b, a lipid antigen-presenting molecule, which is inducibly expressed on monocytes and dendritic cells. Using CD1b tetramers to study multiple donors, we found that many CD1b-specific γδ T cells use Vδ1. D  ...[more]

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