TY - JOUR
T1 - Discovery of an ancient MHC category with both class I and class II features
AU - Okamura, Kazuhiko
AU - Dijkstra, Johannes M.
AU - Tsukamoto, Kentaro
AU - Grimholt, Unni
AU - Wiegertjes, Geert F.
AU - Kondow, Akiko
AU - Yamaguchi, Hisateru
AU - Hashimoto, Keiichiro
PY - 2021/12/21
Y1 - 2021/12/21
N2 - 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.
AB - 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.
KW - Major histocompatibility complex
KW - MHC class divergence
KW - MHC class I
KW - MHC class II
KW - Molecular evolution
U2 - 10.1073/pnas.2108104118
DO - 10.1073/pnas.2108104118
M3 - Article
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 51
M1 - e2108104118
ER -