Small molecule modulators of MHC class II antigen presentation: mechanistic insights and implications for therapeutic application

Antigen presenting cells express MHC class II molecules bound to Peptide Fragments and are responsible for activating CD4(+) T cells that then broadly influence many branches of the immune response. A growing interest in developing strategies to therapeutically influence the Peptides to which naïve CD4(+) T cells are exposed has led to the hunt for small molecules that modulate peptide presentation through the MHC class II pathway. Over the past decade a number of small molecules have been discovered that show surprising diversity in both structure and putative mechanisms. This review discusses how these small molecules were identified and compares the mechanisms by which they may act with what is known about the endogenous peptide exchanger, HLA-DM.