期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：51
DOI：10.1073/pnas.2108104118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
Two classes of major histocompatibility complex (MHC) molecules, MHC class I and class II, play important roles in our immune system, presenting antigens to functionally distinct T lymphocyte populations. However, the origin of this essential MHC class divergence is poorly understood. Here, we discovered a category of MHC molecules (W-category) in the most primitive jawed vertebrates, cartilaginous fish, and also in bony fish and tetrapods. W-category, surprisingly, possesses class II–type α- and β-chain organization together with class I–specific sequence motifs for interdomain binding, and the W-category α2 domain shows unprecedented, phylogenetic similarity with β
2-microglobulin of class I. Based on the results, we propose a model in which the ancestral MHC class I molecule evolved from class II–type W-category. The discovery of the ancient MHC group, W-category, sheds a light on the long-standing critical question of the MHC class divergence and suggests that class II type came first.
关键词：major histocompatibility complex; MHC class divergence; MHC class I; MHC class II; molecular evolution
