Presentation of glycolipid antigens by mouse and human CD1 molecules to NK T cells

Natural killer (NK) T cells are a lymphocyte subset that recognizes CD 1. Mouse CD1d1 (mCD1d1) is able to present the glycolipid antigen alpha-galactosylceramide (alpha-GalCer) to mouse NK T cells. Recognition of alpha-GalCer requires expression of the invariant V alpha 14 TCR, but is less selective for the expression of a particular beta chain. Human CD1d (hCD1d) is able to present alpha-GalCer to both human and mouse NK T cells, demonstrating the functional conservation of the NK T cell subset. A panel of alpha-GalCer analogs was used to define the requirements for antigen presentation by mCD1d1 and hCD1d. A mouse NK T cell hybridoma and bulk human NK T cells have strikingly similar requirements in terms of antigen recognition. Surprisingly, the nearly complete truncation of the ceramide acyl chain does not affect the NK T cell response to glycolipid presented by either mCD1 or hCD1d, suggesting that only one of the two hydrophobic pockets of the CDI antigen binding groove needs to be filled by antigen, hCD1d does exhibit, however, more stringent requirements for glycolipid antigen presentation than mCD1 in terms of the sphingosine base length and the requirement for a position 4 hydroxyl group.