Immune sensing of microbial glycolipids and related conjugates by T cells and the pattern recognition receptors MCL and Mincle

Microbes produce a wide range of small molecule glycoconjugates that constitute unique molecular signatures. These molecules are recognized by a range of detection systems, triggering immune responses to microbial pathogens and commensals. The antigen-presenting molecules of the CD1 class, CD1a-d, capture lipidic molecules and present them to diverse and innate-like T cell populations including natural killer T cells and germline-encoded mycolyl reactive T cells. The antigen-presenting molecule MR1 captures vitamin B metabolites and presents them to mucosal associated invariant T cells. In both cases, recognition of the small molecule-antigen presenting molecule complexes occurs through T cell receptors on the surface of T lymphocytes. The pattern recognition receptors macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle) receptors sense glycolipids and through signalling initiate cellular activation, shaping immune responses to peptide antigens, including the differentiation of naive T cells into conventional effector T helper cells. In this review, we provide an overview of the diverse structures of immunogenic lipidic molecules and vitamin B metabolites and their recognition by select systems of the immune system. Future advances in our understanding of the roles of such molecules in innate and adaptive immune responses will require the coordinated efforts of synthetic and natural products chemists, immunologists and biologists.