Conventional and non-conventional recognition of non-peptide antigens by Tlymphocytes

For thousands of years, mycobacteria have evolved with vertebrates by paras itizing their immune system. Their intraphagocytic lifestyle enables an esc ape from humoral immunity, while providing an extraordinarily rich and dura ble source of T-cell stimuli. Macrophages can chew out mycobacterial cell w all antigens which, once associated with polymorphic MHC molecules, are pre sented on their cell surface, Upon recognition of these antigens, the react ive T lymphocytes trigger effector responses such as immune help or bacteri al killing that may ultimately protect against infection. So far, the antig ens specifically recognized by the T-cell receptor for antigen (TCR) were t hought to correspond exclusively to small peptidic fragments processed from microbial proteins. However, recent studies have revealed other types of a ntigenic molecules from mycobacteria, but also from other sources, which st imulate strong T-cell responses in humans and in mouse models. These non-pe ptide antigens can be recovered in different structural classes: aliphatic lipid or glycolipids and phosphoantigens. Beside mycobacterial nonpeptidic T-lymphocyte reactivity, another immunological context (allergy) involving T lymphocytes stimulated by an aromatic glycolipid was recently demonstrate d (figure I). This article will briefly review these three distinct categor ies of non-peptide ligands recognized by T cells, which involve atypical pa thways of antigen recognition.