Another Kind of Antigen

The human CD1b groove is composed of four pockets – A', C', F', and T'. Here the two alkyl chains (C16 and C18) of phosphotidylinositol lie in the A' (red) and C' (yellow) pockets, respectively. Two C16 molecules lie in the T' tunnel (violet) and the inositol ring (dark green) protudes from the groove and lies on the predicted region for T-cell receptor binding. (From D.B. Moody, S.A. Procelli, Nat Rev Immunol, 3:11–22, 2003.)

The discovery that lipids can serve as antigens first stunned the immunological community a decade ago. But following the initial shock that floppy, hydrophobic hydrocarbon chains could stir a T-lymphocyte reaction with the same specificity as the peptides presented by conventional major histocompatibility complex (MHC) molecules, researchers hunkered down to determine the new mechanisms.

Now the process and the cast of players, including presentation molecules, loading molecules, and previously undescribed populations of T lymphocytes, are raising ...