Basic science for the clinician 35: CD1, invariant NKT (iNKT) Cells, and gammadelta T-cells

As noted in previous articles in this series, the very heterogeneous MHC class I and II molecules present peptide antigens to T-cells. However, there is another family of less heterogeneous MHC-related molecules. CD1 molecules present lipid antigens, oftentimes to 2 other distinct families of T-cells: gammadelta T-cells (named because they bear a T-cell antigen receptor consisting of a gamma chain and a delta chain rather than the alpha chain/beta chain heterodimer on most T-cells) and iNKT cells (T-cells that bear markers previously defined on natural killer cells). CD1 molecules and the gammadelta T-cells and iNKT cells to which they present antigens have fundamental responsibilities for immune surveillance over intracellular pathogens and serve other roles that place them at the boundary between innate and acquired immunity. The gammadelta T-cell has been implicated in the pathogenesis of many diseases, rheumatologic and otherwise, suggesting that better understanding of these cells, and of CD1 molecules, may help us explain the immunopathogenesis of some inflammatory diseases and how to craft more targeted therapies in many fields of medicine.