Abstract
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.
Highlights
Major histocompatibility complex j major histocompatibility complex (MHC) class divergence j MHC class I j MHC class indicated by (I) and (II) j molecular evolution [3]
We discovered a category of MHC molecules which possesses dual nature regarding the two MHC classes and, appears to be critical for the elucidation of the class diversification
As we succeeded in isolating the authentic classical MHC class I genes from banded houndshark [17], this singleexon sequence became an enigma
Summary
Major histocompatibility complex j MHC class divergence j MHC class I j MHC class II j molecular evolution [3].
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