Processing of glycans on glycoprotein and glycopeptide antigens in antigen-presenting cells

Until about 12 years ago, almost all experimental work with antigens capable of stimulating T cells had been performed with proteins and peptides, as well as haptenated proteins and peptides. By far most of the work had been performed with mice that had been immunized and examined for responses in assays for T cell proliferation. Pure carbohydrates were found to be incapable of major histocompatibility complex (MHC) binding and T cell stimulation (1, 2). However, within the last 10 years it has become evident that both CD4+ and CD8+ T cells can recognize glycopeptides carrying mono- and disaccharides in a MHC-restricted manner provided the glycan group is attached to the peptide at suitable positions. In such glycopeptides, the primed T cells recognize the glycan structure with high fidelity (see below). The question of T cell recognition of glycopeptides may be important in the immune defense against microorganisms, because many microbial antigens are in fact glycosylated. T cell recognition of glycans may also play an important role in the immune defence against tumors, because one of the most consistent traits of a cancer cell is an abnormal glycosylation of the proteins of the malignant cell (3). In this issue of PNAS, Backlund et al. (4) provide evidence that T cell recognition of protein glycans may be crucial also for T cell responses to autoantigens in the course of autoimmune diseases. Below we will describe and discuss the general rules for MHC class II restricted T cell recognition of glycans, the fate of glycoprotein glycans during antigen processing, and the role of antigen glycosylation in tolerance to autoantigens and tumor antigens. T cell recognition of glycans may be crucial for T cell responses to autoantigens.