The versatility of the CD1 lipid antigen presentation pathway

The family of non-classical major histocompatibility complex (MHC) class-I like CD1 molecules has an emerging role in human disease. Group 1 CD1 includes CD1a, CD1b and CD1c, which function to display lipids on the cell surface of antigen-presenting cells for direct recognition by T-cells. The recent advent of CD1 tetramers and the identification of novel lipid ligands has contributed towards the increasing number of CD1-restricted T-cell clones captured. These advances have helped to identify novel donor unrestricted and semi-invariant T-cell populations in humans and new mechanisms of T-cell recognition. However, although there is an opportunity to design broadly acting lipids and harness the therapeutic potential of conserved T-cells, knowledge of their role in health and disease is lacking. We briefly summarize the current evidence implicating group 1 CD1 molecules in infection, cancer and autoimmunity and show that although CD1 are not as diverse as MHC, recent discoveries highlight their versatility as they exhibit intricate mechanisms of antigen presentation.