The intricacies of self-lipid antigen presentation by CD1b

The CD1 family of glycoproteins are MHC class I-like molecules that present a wide array of self and foreign lipid antigens to T-cell receptors (TCRs) on T-cells. Humans express three classes of CD1 molecules, denoted as Group 1 (CD1a, CD1b, and CD1c), Group 2 (CD1d), and Group 3 (CD1e). Of the CD1 family of molecules, CD1b exhibits the largest and most complex antigen binding groove; allowing it the capabilities to present a broad spectrum of lipid antigens. While its role in foreign-lipid presentation in the context of mycobacterial infection are well characterized, understanding the roles of CD1b in autoreactivity are recently being elucidated. While the mechanisms governing proliferation of CD1b-restricted autoreactive T cells, regulation of CD1 gene expression, and the processes controlling CD1+ antigen presenting cell maturation are widely undercharacterized, the exploration of self-lipid antigens in the context of disease have recently come into focus. Furthermore, the recently expanded pool of CD1b crystal structures allow the opportunity to further analyze the molecular mechanisms of T-cell recognition and self-lipid presentation; where the intricacies of the two-compartment system, that accommodate both the presented self-lipid antigen and scaffold lipids, are scrutinized. This review delves into the immunological and molecular mechanisms governing presentation and T-cell recognition of the broad self-lipid repertoire of CD1b; with evidence mounting pointing towards a role in diseases such as microbial infection, autoimmune diseases, and cancer.