TCR-mediated recognition of glycolipid CD1 complexes

Populations of unconventional T lymphocytes that express alpha beta T cell antigen receptors (TCRs) have been characterized, including T cells reactive to glycolipids presented by CD1 molecules. The CD1 molecules have a structure broadly similar to major histocompatibility complex (MHC) class I and class II proteins, but because the antigens CD 1 presents are so different from peptides, it is possible that glycolipid reactive TCRs have properties that distinguish them from TCRs expressed by conventional T cells. Consistent with this possibility, CD1-reactive T cells have an unrestrained pattern of co-receptor expression, as they include CD4+, CD8+, and double-negative cells. Furthermore, unlike peptide-reactive T cells, there are populations of glycolipid-reactive T cells with invariant alpha chain TCRs that are conserved across species. There are also glycolipid reactive populations with more variable TCRs, however, suggesting that it may be difficult to make categorical generalizations about glycolipid reactive TCRs. Among the glycolipid reactive TCRs, the invariant TCR expressed by CD1d reactive NKT cells has been by far the most thoroughly studied, and in this article we emphasize the unique features of this antigen recognition system, including repertoire formation, fine specificity, TCR affinity, and TCR structure.