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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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(a) 51Cr release assay of NKG7 against LCL721.221 (•),  LCL721.221.G (○), C1R (▾), C1R-B*2705 (▿), and C1R-B*5101 (▪);  (b) 51Cr assay of NKG7 against LCL721.221 (•), LCL721.221.G (○),  STEMO (▾), and PHA blasts of PBL of a HLA-A3+, -B7+ and -Cw7+  donor (▿).
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Figure 6: (a) 51Cr release assay of NKG7 against LCL721.221 (•), LCL721.221.G (○), C1R (▾), C1R-B*2705 (▿), and C1R-B*5101 (▪); (b) 51Cr assay of NKG7 against LCL721.221 (•), LCL721.221.G (○), STEMO (▾), and PHA blasts of PBL of a HLA-A3+, -B7+ and -Cw7+ donor (▿).

Mentions: To examine whether HLA-G inhibition of the NK lines is mediated versus NKAT3 or NKAT4 reactivity of these lines, targets expressing NKAT3 or NKAT4 ligands were tested. Fig. 6 shows representative data obtained with the NKG7 line for recognition of (a) HLA-B*2705 or -B*5101-transfected C1R cells and (b) HLA-A3-expressing cells (STEMO and HLA-A3+ PHA blasts). C1R, which is reduced in MHC class I expression, was found to be killed by the NK lines just as efficiently as LCL721.221 (Fig. 6 a). Only target cells expressing the HLA-B*2705/-B*5101 alleles inhibited the activity of the NK lines. This set of data suggests that HLA-G inhibition of NKG1, NKG2, and NKG7 runs parallel to inhibition by HLA-B*2705 and -B*5101, both of which carry the HLA-Bw4 public epitope. As shown in Table 1, HLA-Bw4 is recognized by the NKAT3 inhibitory human NK receptor, while HLA-A3 reacts with NKAT4. In conclusion, HLA-G inhibition of NKG1, NKG2, and NKG7 can be blocked by the 5.133 antibody that recognizes NKAT3 as well as NKAT4, but only NKAT3 seems to mediate the inhibition of the NK lines, because they alone can be inhibited by HLA-Bw4 but not HLA-A*0301-bearing targets.


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)

(a) 51Cr release assay of NKG7 against LCL721.221 (•),  LCL721.221.G (○), C1R (▾), C1R-B*2705 (▿), and C1R-B*5101 (▪);  (b) 51Cr assay of NKG7 against LCL721.221 (•), LCL721.221.G (○),  STEMO (▾), and PHA blasts of PBL of a HLA-A3+, -B7+ and -Cw7+  donor (▿).
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Related In: Results  -  Collection

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Figure 6: (a) 51Cr release assay of NKG7 against LCL721.221 (•), LCL721.221.G (○), C1R (▾), C1R-B*2705 (▿), and C1R-B*5101 (▪); (b) 51Cr assay of NKG7 against LCL721.221 (•), LCL721.221.G (○), STEMO (▾), and PHA blasts of PBL of a HLA-A3+, -B7+ and -Cw7+ donor (▿).
Mentions: To examine whether HLA-G inhibition of the NK lines is mediated versus NKAT3 or NKAT4 reactivity of these lines, targets expressing NKAT3 or NKAT4 ligands were tested. Fig. 6 shows representative data obtained with the NKG7 line for recognition of (a) HLA-B*2705 or -B*5101-transfected C1R cells and (b) HLA-A3-expressing cells (STEMO and HLA-A3+ PHA blasts). C1R, which is reduced in MHC class I expression, was found to be killed by the NK lines just as efficiently as LCL721.221 (Fig. 6 a). Only target cells expressing the HLA-B*2705/-B*5101 alleles inhibited the activity of the NK lines. This set of data suggests that HLA-G inhibition of NKG1, NKG2, and NKG7 runs parallel to inhibition by HLA-B*2705 and -B*5101, both of which carry the HLA-Bw4 public epitope. As shown in Table 1, HLA-Bw4 is recognized by the NKAT3 inhibitory human NK receptor, while HLA-A3 reacts with NKAT4. In conclusion, HLA-G inhibition of NKG1, NKG2, and NKG7 can be blocked by the 5.133 antibody that recognizes NKAT3 as well as NKAT4, but only NKAT3 seems to mediate the inhibition of the NK lines, because they alone can be inhibited by HLA-Bw4 but not HLA-A*0301-bearing targets.

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