title: A major allogenic leukocyte antigen in the agnathan hagfish.
abstract: 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.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takaba
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imai
authors.forename: Shoji
authors.initials: S
authors.lastname: Miki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Morishita
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miyashita
authors.forename: Naoko
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nishizumi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakano
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D006196:Hagfishes / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D011946:Receptors, Antigen / Q000276:immunology
chemical_list: D000906:Antibodies; D006649:Histocompatibility Antigens; D008565:Membrane Proteins; D011946:Receptors, Antigen