Blastocyst MHC, a putative murine homologue of HLA-G, protects TAP-deficient tumor cells from natural killer cell-mediated rejection in vivo.
Blastocyst MHC is a recently identified mouse MHC class Ib gene, which is selectively expressed in blastocyst and placenta, and may be the mouse homolog of HLA-G gene the products of which have been implicated in protection of fetal trophoblasts from maternal NK cells and evasion of some tumor cells from NK cell attack. In this study, we identified two blastocyst MHC gene transcripts encoding a full-length alpha-chain (bc1) and an alternatively spliced form lacking the alpha2 domain (bc2), which may be homologous to HLA-G1 and HLA-G2, respectively. Both placenta and a teratocarcinoma cell line predominantly expressed the bc2 transcript. When these cDNAs were expressed in TAP-deficient RMA-S or TAP-sufficient RMA cells, only bc1 protein was expressed on the surface of RMA cells, but both bc1 and bc2 proteins were retained in the cytoplasm of RMA-S cells. Significantly, the RMA-S cells expressing either bc1 or bc2 were protected from lysis by NK cells in vitro. This protection was at least partly mediated by up-regulation of Qa-1(b) expression on the surface of RMA-S cells, which engaged the CD94/NKG2A inhibitory receptor on NK cells. More importantly, the bc1- or bc2-expressing RMA-S cells were significantly protected from NK cell-mediated rejection in vivo. These results suggested a role for blastocyst MHC in protecting TAP-deficient trophoblasts and tumor cells from NK cell attack in vivo.
Tajima
Atsushi
A
Department of Immunology and Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.
Tanaka
Toshitaka
T
Ebata
Tomohiko
T
Takeda
Kazuyoshi
K
Kawasaki
Akemi
A
Kelly
Janice M
JM
Darcy
Phillip K
PK
Vance
Russell E
RE
Raulet
David H
DH
Kinoshita
Katsuyuki
K
Okumura
Ko
K
Smyth
Mark J
MJ
Yagita
Hideo
H
D017398:Alternative Splicing / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001755:Blastocyst / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006680:HLA Antigens / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000502:physiology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins; D011247:Pregnancy; D020033:Protein Isoforms / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; C527057:Klrc1 protein, mouse; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009687:Nuclear Proteins; D020033:Protein Isoforms; C032907:Q surface antigens; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C064655:V(D)J recombination activating protein 2