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Publication Abstract from PubMed

CD1a is a monomorphic antigen-presenting molecule on dendritic cells that presents lipids to alphabeta T cells. Whether CD1a represents a ligand for other immune receptors remains unknown. Here we use CD1a tetramers to show that CD1a is a ligand for Vdelta1(+) gammadelta T cells. Functional studies suggest that two gammadelta T cell receptors (TCRs) bound CD1a in a lipid-independent manner. The crystal structures of three Vgamma4Vdelta1 TCR-CD1a-lipid complexes reveal that the gammadelta TCR binds at the extreme far side and parallel to the long axis of the beta-sheet floor of CD1a's antigen-binding cleft. Here, the gammadelta TCR co-recognises the CD1a heavy chain and beta2 microglobulin in a manner that is distinct from all other previously observed gammadelta TCR docking modalities. The 'sideways' and lipid antigen independent mode of autoreactive CD1a recognition induces TCR clustering on the cell surface and proximal T cell signalling as measured by CD3zeta phosphorylation. In contrast with the 'end to end' binding of alphabeta TCRs that typically contact carried antigens, autoreactive gammadelta TCRs support geometrically diverse approaches to CD1a, as well as antigen independent recognition.

Atypical sideways recognition of CD1a by autoreactive gammadelta T cell receptors.,Wegrecki M, Ocampo TA, Gunasinghe SD, von Borstel A, Tin SY, Reijneveld JF, Cao TP, Gully BS, Le Nours J, Moody DB, Van Rhijn I, Rossjohn J Nat Commun. 2022 Jul 5;13(1):3872. doi: 10.1038/s41467-022-31443-9. PMID:35790773^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.