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

Kazuhiko Okamura, Johannes M. Dijkstra, Kentaro Tsukamoto, Unni Grimholt, Geert F. Wiegertjes, Akiko Kondo, Hisateru Yamaguchi, Keiichiro Hashimoto

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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 β2-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.

Original languageEnglish
Article numbere2108104118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
Publication statusPublished - 21-12-2021

All Science Journal Classification (ASJC) codes

  • General


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