Antigen unfolding and disulfide reduction in antigen presenting cells

CD4+ helper T cells recognize short peptides stably associated with class II MHC molecules displayed on the surface of antigen presenting cells. Very little is known about the sequence of events that lead to the generation of these peptides from protein antigens. It is likely that native proteins must partially unfold before they are cleaved by endopeptidases or bind to MHC proteins. For many antigens, the rate-limiting step in unfolding may involve reduction of disulfide bonds. Evidence that disulfide reduction occurs in endocytic compartments is reviewed and potential mechanisms for the reduction of antigen disulfide bonds are proposed.