Recognition of nonclassical HLA class I antigens by gamma delta T cells during pregnancy.
The healthy trophoblast does not express classical HLA-A and HLA-B products; therefore, an MHC-restricted recognition of trophoblast-presented Ags is unlikely. In the decidua and also in peripheral blood of healthy pregnant women, gammadelta T cells significantly increase in number. We investigated the possible role of gammadelta T cells in recognition of trophoblast-presented Ags. PBL and isolated gammadelta T cells from healthy pregnant women as well as from those at risk for premature pregnancy termination were conjugated to choriocarcinoma cells (JAR) transfected with nonclassical HLA Ags (HLA-E, HLA-G). To investigate the involvement of killer-inhibitory/killer-activatory receptors in trophoblast recognition, we tested the effect of CD94 block on cytotoxic activity of Vdelta2(+) enriched gammadelta T cells to HLA-E- and/or HLA-G-transfected targets. Lymphocytes from healthy pregnant women preferentially recognized HLA(-) choriocarcinoma cells, whereas those from pathologically pregnant patients did not discriminate between HLA(+) and HLA(-) cells. Normal pregnancy Vdelta2(+) T cells conjugated at a significantly increased rate to HLA-E transfectants, whereas Vdelta2(+) lymphocytes from pathologically pregnant women did not show a difference between those and HLA(-) cells. Blocking of the CD94 molecule of Vdelta2(+) lymphocytes from healthy pregnant women resulted in an increased cytotoxic activity to HLA-E-transfected target cells. These data indicate that Vdelta2(+) lymphocytes of healthy pregnant women recognize HLA-E on the trophoblast, whereas Vdelta1 cells react with other than HLA Ags. In contrast to Vdelta2(+) lymphocytes from healthy pregnant women, those from women with pathological pregnancies do not recognize HLA-E via their killer-inhibitory receptors and this might account for their high cytotoxic activity.
Barakonyi
Aliz
A
Department of Medical Microbiology and Immunology, Pecs University, Medical School, Pecs, Hungary.
Kovacs
Katalin T
KT
Miko
Eva
E
Szereday
Laszlo
L
Varga
Peter
P
Szekeres-Bartho
Julia
J
D000022:Abortion, Spontaneous / Q000276:immunology; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002822:Choriocarcinoma / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000378:metabolism* / Q000502:physiology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism* / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000276:immunology; D000097625:HLA-E Antigens
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011257:Pregnancy Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human