Human γδ T cells recognize CD1b by two distinct mechanisms

Reijneveld, Josephine F., Ocampo, Tonatiuh A., Shahine, Adam, Gully, Benjamin S., Vantourout, Pierre, Hayday, Adrian C., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Moody, D. Branch and Van Rhijn, Ildiko 2020. Human γδ T cells recognize CD1b by two distinct mechanisms. Proceedings of the National Academy of Sciences 117 (37) , pp. 22933-22952. 10.1073/pnas.2010545117

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Abstract

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. Despite their common use of Vδ1, three CD1b-specific γδ 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 Vγ segments were present among the CD1b-specific TCRs, but chain swap experiments demonstrated that CD1b specificity was mediated by the Vδ1 chain. One of the CD1b-specific Vδ1+ TCRs paired with Vγ4 and shows dual reactivity to CD1b and butyrophilin-like proteins. αβ 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	Full text licensed under CC BY 4.0
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Date of First Compliant Deposit:	30 October 2020
Date of Acceptance:	7 August 2020
Last Modified:	03 May 2023 15:12
URI:	https://orca.cardiff.ac.uk/id/eprint/136031

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