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Human histocompatibility leukocyte antigen (HLA)-G molecules inhibit NKAT3 expressing natural killer cells.

Münz C, Holmes N, King A, Loke YW, Colonna M, Schild H, Rammensee HG - J. Exp. Med. (1997)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Tübingen, Federal Republic of Germany.

ABSTRACT
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.

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51Cr release assay of CD56+ PBL versus LCL721.221 (•), as  well as LCL721.221.G (○), and CD56− PBL versus LCL721.221(▾).
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Figure 1: 51Cr release assay of CD56+ PBL versus LCL721.221 (•), as well as LCL721.221.G (○), and CD56− PBL versus LCL721.221(▾).

Mentions: The effect of HLA-G transfection on killing by CD56+ NK cultures was investigated using the HLA- human lymphoblastoid cell line LCL721.221 with and without HLA-G transfection as targets for positively MACS-selected CD56+ PBL of healthy donors. CD56+ PBL show the phenotype of peripheral NK cells by FACS® analysis: CD16+, CD56dim, CD4− and partial CD8 expression (data not shown). Our HLA-G transfectant of the LCL721.221 cell line, LCL721.221.G, expresses the nonclassical MHC class I molecule with a mean fluorescence value of 45–50 (14). In a 4-h 51Cr release assay, the specific lysis of LCL721.221 mediated by the isolated NK population against LCL721.221 was between 70–80% at a E/T ratio of 1:1 (Fig. 1). At the same ratio, the killing of LCL721.221.G was remarkably reduced (to 40–45%; Fig. 1). In both cases, the killing decreased with lower E/T ratios. The CD56− PBL population showed only low background killing of both cell lines (around 10% specific lysis; Fig. 1).


Human histocompatibility leukocyte antigen (HLA)-G molecules inhibit NKAT3 expressing natural killer cells.

Münz C, Holmes N, King A, Loke YW, Colonna M, Schild H, Rammensee HG - J. Exp. Med. (1997)

51Cr release assay of CD56+ PBL versus LCL721.221 (•), as  well as LCL721.221.G (○), and CD56− PBL versus LCL721.221(▾).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196038&req=5

Figure 1: 51Cr release assay of CD56+ PBL versus LCL721.221 (•), as well as LCL721.221.G (○), and CD56− PBL versus LCL721.221(▾).
Mentions: The effect of HLA-G transfection on killing by CD56+ NK cultures was investigated using the HLA- human lymphoblastoid cell line LCL721.221 with and without HLA-G transfection as targets for positively MACS-selected CD56+ PBL of healthy donors. CD56+ PBL show the phenotype of peripheral NK cells by FACS® analysis: CD16+, CD56dim, CD4− and partial CD8 expression (data not shown). Our HLA-G transfectant of the LCL721.221 cell line, LCL721.221.G, expresses the nonclassical MHC class I molecule with a mean fluorescence value of 45–50 (14). In a 4-h 51Cr release assay, the specific lysis of LCL721.221 mediated by the isolated NK population against LCL721.221 was between 70–80% at a E/T ratio of 1:1 (Fig. 1). At the same ratio, the killing of LCL721.221.G was remarkably reduced (to 40–45%; Fig. 1). In both cases, the killing decreased with lower E/T ratios. The CD56− PBL population showed only low background killing of both cell lines (around 10% specific lysis; Fig. 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Tübingen, Federal Republic of Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus