CD1d presentation of glycolipids

The CD1 family of antigen-presenting molecules consists of five members, CD1a to e. Of these molecules CD1d has been the subject of much interest over the past 10 years following the discovery that this molecule presents antigens to a group of T cells known as invariant natural killer T cells (iNKT). iNKT cells carry an invariant T cell receptor which contains homologous gene segments in mouse and man. iNKT cells are positively selected in the thymus in the same manner as major histocompatibility complex restricted T cells, except iNKT cells require CD1d to be presented by thymocytes rather than epithelial cells. Once in peripheral organs, iNKT cells appear to play multiple roles in host defence against pathogens and cancer. If the numbers of iNKT cells are not correctly regulated it can result in autoimmune disorders, such as diabetes. The ligands for iNKT cells have been the subject of much research but identifying physiologically relevant candidate ligands for positive selection or activation has proved technically very challenging. This is largely due to the fact that the ligands for iNKT cells are lipids. The lipid ligands for thymic selection and some of those involved in peripheral activation are self-derived. Glycosphingolipids are suggested to be the class of lipid for iNKT cell thymic development. For peripheral activation it appears multiple classes of self-derived lipids may play a role, in addition to pathogen-derived lipids. This review will cover essential background to iNKT cell and CD1d biology with emphasis on the candidate iNKT cell ligands proposed to date.