Abstract
The presentation of small protein fragments, both foreign and native, on the surface of specialized cells is one of the cornerstones of our immune system. In complex with MHC binding proteins, these protein antigens will be recognized by T-cell membrane receptors either as self or non-self, and an appropriate response will be initiated. In recent years it has become apparent that immune responses may also be induced by a diverse array of lipid antigens. The presentation of these antigens involves a class of binding proteins referred to as CD1, analogous to MHC proteins. The CD1 family includes 5 isoforms of distinct specificity, of which CD1a, CD1b and CD1d have been characterized structurally in complex with diverse lipid antigens. Here we report the results of extensive computer simulation studies of this family, from which we gain insights into the mechanism of lipid binding. We also present a molecular model of CD1c, and based on this, rationalize its specificity for branched mycobacterial lipids.
