Discovery of an ancient MHC category with both class I and class II features

Significance Two classes of major histocompatibility complex (MHC) molecules, MHC class I and MHC class II, constitute the basis of our elaborate, adaptive immune system as antigen-presenting molecules. They perform distinct, critical functions: especially, MHC class I in case of antivirus and antitumor defenses, and MHC class II, in case of effective antibody responses. This important class diversification has long been enigmatic, as vestiges of the evolutionary molecular changes have not been found. The revealed ancient MHC category represents a plausible intermediate group between the two classes, and the data suggest that class II preceded class I in molecular evolution. Fundamental understanding of the molecular evolution of MHC molecules should contribute to understanding the basis of our complex biological defense system.