A structural perspective of how T cell receptors recognize the CD1 family of lipid antigen–presenting molecules

• Published in: The Journal of biological chemistry Vol. 300; no. 8; p. 107511
• Main Authors: Cao, Thinh-Phat, Shahine, Adam, Cox, Liam R., Besra, Gurdyal S., Moody, D. Branch, Rossjohn, Jamie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: antigen presentation; CD1; lipid; lipid analog; structure; T cell recognition; TCR; antigen presentation; Ag; MHC; MPM; lipid; structure; CD1; lipid analog; NKT; T cell recognition; SM; PM; αGalCer
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1016/j.jbc.2024.107511

The CD1 family of antigen-presenting molecules adopt a major histocompatibility complex class I (MHC-I) fold. Whereas MHC molecules present peptides, the CD1 family has evolved to bind self- and foreign-lipids. The CD1 family of antigen-presenting molecules comprises four members—CD1a, CD1b, CD1c, and CD1d—that differ in their architecture around the lipid-binding cleft, thereby enabling diverse lipids to be accommodated. These CD1–lipid complexes are recognized by T cell receptors (TCRs) expressed on T cells, either through dual recognition of CD1 and lipid or in a new model whereby the TCR directly contacts CD1, thereby triggering an immune response. Chemical syntheses of lipid antigens, and analogs thereof, have been crucial in understanding the underlying specificity of T cell–mediated lipid immunity. This review will focus on our current understanding of how TCRs interact with CD1–lipid complexes, highlighting how it can be fundamentally different from TCR-MHC-peptide corecognition.