Impact of glycans on T-cell tolerance to glycosylated self-antigens

There is now substantial evidence that antigen post-translational modifications are recognized by T cells, and alterations in epitope modification has been linked to a number of autoimmune diseases. An estimated one third of the MHC ligands contain post-translational modification of epitopes. A common post-translational modification of proteins is glycosylation and it is predicted on theoretical grounds that similar to 1-5% of MHC ligands may bear a glycan. From numerous studies over the past 15 years it is clear that glycans can influence T cell responses either by contribution to the structure of the epitope or by influencing the profile of peptide epitopes presented by APCs. The influence of glycans on antigen processing and T cell recognition has particular relevance to the induction of tolerance to self-antigens. Here we discuss the potential impact of glycans on the profile of self-epitopes presented by APCs and the consequence of changes in glycosylation to generate neo self-epitopes resulting in the loss of tolerance and the development of autoimmune diseases. With the recent developments in profiling T cell epitopes, and with strategies for modulating glycosylation in vivo, it is now feasible to directly examine the global influence of glycans on self-tolerance and autoimmunity.