A major allogenic leukocyte antigen in the agnathan hagfish

Hiroyuki Takaba, Takeshi Imai, Shoji Miki, Yasuyuki Morishita, Akihiro Miyashita, Naoko Ishikawa, Hirofumi Nishizumi, Hitoshi Sakano

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


All vertebrates, from jawless fish to mammals, possess adaptive immune systems that can detect and inactivate non-self-antigens through a vast repertoire of antigen receptors. Unlike jawed vertebrates, the hagfish utilizes variable lymphocyte receptors (VLRs) that are unrelated to immunoglobulin molecules but are diversified by copy-choice gene conversion mechanism. Here, we report that hagfish VLRs react with allogenic leukocyte antigens but not with self-antigens. We found that a highly polymorphic membrane protein, NICIR3, is recognized by VLRs as an allogenic leukocyte antigen (ALA). In a serological cross-reactivity test, a close correlation was observed between the amino acid differences in the protein sequences and the VLR cross-reactivities. This leukocyte antigen was predominantly expressed in phagocytic leukocytes, where it was associated with phagocytosed protein antigens. These findings suggest that a polymorphic leukocyte antigen, NICIR3/ALA, plays a pivotal role in jawless vertebrate adaptive immunity.

Original languageEnglish
Article number1716
JournalScientific reports
Publication statusPublished - Apr 24 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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