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Recognition of Nonclassical HLA Class I Antigens by T Cells During Pregnancy¹

Aliz Barakonyi^*, Katalin T. Kovacs^*, Eva Miko^*, Laszlo Szereday^*, Peter Varga and Julia Szekeres-Bartho^2,*

^* Department of Medical Microbiology and Immunology, Pecs University, Medical School, Pecs, Hungary; and Department of Obstetrics and Gynecology, County Hospital, Pecs, Hungary.

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, T cells significantly increase in number. We investigated the possible role of T cells in recognition of trophoblast-presented Ags. PBL and isolated 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 V2⁺ enriched 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 V2⁺ T cells conjugated at a significantly increased rate to HLA-E transfectants, whereas V2⁺ lymphocytes from pathologically pregnant women did not show a difference between those and HLA^- cells. Blocking of the CD94 molecule of V2⁺ lymphocytes from healthy pregnant women resulted in an increased cytotoxic activity to HLA-E-transfected target cells. These data indicate that V2⁺ lymphocytes of healthy pregnant women recognize HLA-E on the trophoblast, whereas V1 cells react with other than HLA Ags. In contrast to V2⁺ 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.

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