Human histocompatibility leukocyte antigen (HLA)-G molecules inhibit NKAT3 expressing natural killer cells.
The crucial immunological function of the classical human major histocompatibility complex (MHC) class I molecules, human histocompatibility leukocyte antigen (HLA)-A, -B, and -C, is the presentation of peptides to T cells. A secondary function is the inhibition of natural killer (NK) cells, mediated by binding of class I molecules to NK receptors. In contrast, the function of the nonclassical human MHC class I molecules, HLA-E, -F, and -G, is still a mystery. The specific expression of HLA-G in placental trophoblast suggests an important role for this molecule in the immunological interaction between mother and child. The fetus, semiallograft by its genotype, escapes maternal allorecognition by downregulation of HLA-A and HLA-B molecules at this interface. It has been suggested that the maternal NK recognition of this downregulation is balanced by the expression of HLA-G, thus preventing damage to the placenta. Here, we describe the partial inhibition of NK lysis of the MHC class I negative cell line LCL721.221 upon HLA-G transfection. We present three NK lines that are inhibited via the interaction of their NKAT3 receptor with HLA-G and with HLA-Bw4 molecules. Inhibition can be blocked by the anti-NKAT3 antibody 5.133. In conclusion, NK inhibition by HLA-G via NKAT3 may contribute to the survival of the fetal semiallograft in the mother during pregnancy.
Münz
C
C
Department of Immunology, University of Tübingen, Federal Republic of Germany.
Holmes
N
N
King
A
A
Loke
Y W
YW
Colonna
M
M
Schild
H
H
Rammensee
H G
HG
D002478:Cells, Cultured; D006680:HLA Antigens / Q000502:physiology*; D015234:HLA-A Antigens / Q000502:physiology; D015235:HLA-B Antigens / Q000502:physiology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D014162:Transfection
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C515083:KIR3DL1 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1