Diverse antigen presentation by the Group 1 CD1 molecule, CD1c

CD1 molecules are Major Histocompatibility Complex (MHC) class I-like proteins that present diverse lipid antigens to T cells. Most of our understanding of CD1 lipid presentation and T cell recognition has come from study of the invariant Natural Killer T cell recognition of CD1d. However, in addition to CD1d, humans possess three additional CD1 molecules: CD1a, CD1b and CD1c, referred to as the Group 1 CD1s. The lack of an appropriate murine molecule to probe the function and disease relevance of these molecules has hindered understanding their precise immunological role, despite their pivotal role in human immunity. In this perspective, we discuss the progress of functional and molecular studies of CD1c. CD1c has been shown to specifically present lipids from Mycobacterium tuberculosis and other related pathogenic mycobacteria. αβ T cells reactive to these lipids presented in the context of CD1c have been characterized and upon stimulation secrete IFN-γ, an important cytokine in tuberculosis disease clearance. Other ligands characterized for CD1c include PI and PC, a lipopeptide with a dodecameric peptide moiety and sulfatides. These structurally and chemically diverse ligands suggest that CD1c has the capacity to present a wide repertoire of antigens to reactive T cells. Indeed, a substantial percentage (∼2%) of the circulating αβ T cell population is reactive to CD1c presenting endogenous antigens, suggesting that this particular Group 1 molecule may play an important role in the human immune response.