The Alpha1 Domain of HLA-G1 and HLA-G2 Inhibits Cytotoxicity Induced by Natural Killer Cells: is HLA-G the Public Ligand for Natural Killer Cell Inhibitory Receptors?

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1997 May 13

PMID 9144223

Citations 86

Authors

N Rouas-Freiss

R E Marchal

M Kirszenbaum

J Dausset

E D Carosella

Affiliations

Soon will be listed here.

Abstract

We have investigated the protective role of the membrane-bound HLA-G1 and HLA-G2 isoforms against natural killer (NK) cell cytotoxicity. For this purpose, HLA-G1 and HLA-G2 cDNAs were transfected into the HLA class I-negative human K562 cell line, a known reference target for NK lysis. The HLA-G1 protein, encoded by a full-length mRNA, presents a structure similar to that of classical HLA class I antigens. The HLA-G2 protein, deduced from an alternatively spliced transcript, consists of the alpha1 domain linked to the alpha3 domain. In this study we demonstrate that (i) HLA-G2 is present at the cell surface as a truncated class I molecule associated with beta2-microglobulin; (ii) NK cytolysis, observed in peripheral blood mononuclear cells and in polyclonal CD3(-) CD16(+) CD56(+) NK cells obtained from 20 donors, is inhibited by both HLA-G1 and HLA-G2; this HLA-G-mediated inhibition is reversed by blocking HLA-G with a specific mAb; this led us to the conjecture that HLA-G is the public ligand for NK inhibitory receptors (NKIR) present in all individuals; (iii) the alpha1 domain common to HLA-G1 and HLA-G2 could mediate this protection from NK lysis; and (iv) when transfected into the K562 cell line, both HLA-G1 and HLA-G2 abolish lysis by the T cell leukemia NK-like YT2C2 clone due to interaction between the HLA-G isoform on the target cell surface and a membrane receptor on YT2C2. Because NKIR1 and NKIR2, known to interact with HLA-G, were undetectable on YT2C2, we conclude that a yet-unknown specific receptor for HLA-G1 and HLA-G2 is present on these cells.

Citing Articles

The Biological Significance of Trogocytosis.

Agbakwuru D, Wetzel S Results Probl Cell Differ. 2024; 73:87-129.

PMID: 39242376 PMC: 11784324. DOI: 10.1007/978-3-031-62036-2_5.

Conventional and non-conventional antigen presentation by mast cells.

Tung C, Rathore A, St John A Discov Immunol. 2024; 2(1):kyad016.

PMID: 38567067 PMC: 10917180. DOI: 10.1093/discim/kyad016.

Evaluation of HLA-G 14bp Ins/Del and +3142 C/G Polymorphisms in Type 1 Diabetes among South Indian Population.

Gunavathy N, Asirvatham A, Chitra A, Jayalakshmi M Indian J Endocrinol Metab. 2023; 27(3):223-229.

PMID: 37583409 PMC: 10424110. DOI: 10.4103/ijem.ijem_7_22.

Natural Killer Cell Derived Microvesicles Affect the Function of Trophoblast Cells.

Sokolov D, Gorshkova A, Markova K, Milyutina Y, Pyatygina K, Zementova M Membranes (Basel). 2023; 13(2).

PMID: 36837716 PMC: 9963951. DOI: 10.3390/membranes13020213.

Sequence Variations Within and Genomic Segments at the Human Leukocyte Antigen Telomeric End Associated With Acute Graft-Versus-Host Disease in Unrelated Bone Marrow Transplantation.

Suzuki S, Morishima S, Murata M, Tanaka M, Shigenari A, Ito S Front Immunol. 2022; 13:938206.

PMID: 35935961 PMC: 9351719. DOI: 10.3389/fimmu.2022.938206.

References

Carosella E, Kirszenbaum M, Dausset J . [HLA-G: a non classical antigen of major histocompatibility complex]. C R Acad Sci III. 1995; 318(8):827-30. View

Kirszenbaum M, Djoulah S, Hors J, Le Gall I, de Oliveira E, Prost S . HLA-G gene polymorphism segregation within CEPH reference families. Hum Immunol. 1997; 53(2):140-7. DOI: 10.1016/S0198-8859(97)00038-4. View

Moreau P, Carosella E, Teyssier M, Prost S, Gluckman E, Dausset J . Soluble HLA-G molecule. An alternatively spliced HLA-G mRNA form candidate to encode it in peripheral blood mononuclear cells and human trophoblasts. Hum Immunol. 1995; 43(3):231-6. DOI: 10.1016/0198-8859(95)00009-s. View

Kirszenbaum M, Moreau P, Teyssier M, Lafon C, Gluckman E, Dausset J . Evidence for the presence of the alternatively spliced HLA-G mRNA forms in human mononuclear cells from peripheral blood and umbilical cord blood. Hum Immunol. 1995; 43(3):237-41. DOI: 10.1016/0198-8859(95)00008-r. View

Phillips J, Chang C, Mattson J, Gumperz J, Parham P, Lanier L . CD94 and a novel associated protein (94AP) form a NK cell receptor involved in the recognition of HLA-A, HLA-B, and HLA-C allotypes. Immunity. 1996; 5(2):163-72. DOI: 10.1016/s1074-7613(00)80492-6. View

Carosella E, Dausset J, Kirszenbaum M . HLA-G revisited. Immunol Today. 1996; 17(9):407-9. DOI: 10.1016/0167-5699(96)30055-8. View

Moreau P, Carosella E, Gluckman E, Gourand L, Prost S, Dausset J . [Alternative transcripts of the MHC of the non-classical class I HLA-G gene in the in trophoblast during the first pregnancy trimester and in the placenta at term]. C R Acad Sci III. 1995; 318(8):837-42. View

Ellis S, Sargent I, Redman C, McMichael A . Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology. 1986; 59(4):595-601. PMC: 1453327. View

King A, Birkby C, Loke Y . Early human decidual cells exhibit NK activity against the K562 cell line but not against first trimester trophoblast. Cell Immunol. 1989; 118(2):337-44. DOI: 10.1016/0008-8749(89)90382-1. View

10.

Ellis S, Palmer M, McMichael A . Human trophoblast and the choriocarcinoma cell line BeWo express a truncated HLA Class I molecule. J Immunol. 1990; 144(2):731-5. View

11.

Kovats S, Main E, Librach C, Stubblebine M, Fisher S, Demars R . A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990; 248(4952):220-3. DOI: 10.1126/science.2326636. View

12.

Yoneda N, Tatsumi E, Kawano S, Teshigawara K, Oka T, Fukuda M . Detection of Epstein-Barr virus genome in natural-killer-like cell line, YT. Leukemia. 1992; 6(2):136-41. View

13.

Pazmany L, Mandelboim O, Vales-Gomez M, Davis D, Reyburn H, Strominger J . Protection from natural killer cell-mediated lysis by HLA-G expression on target cells. Science. 1996; 274(5288):792-5. DOI: 10.1126/science.274.5288.792. View

14.

Teyssier M, Bensussan A, Kirszenbaum M, Moreau P, Gluckman E, Dausset J . Natural killer cells are the unique lymphocyte cell subset which do not express HLA-G. Nat Immun. 1995; 14(5-6):262-70. View

15.

Ishitani A, Geraghty D . Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci U S A. 1992; 89(9):3947-51. PMC: 525608. DOI: 10.1073/pnas.89.9.3947. View

16.

Colonna M, Spies T, Strominger J, Ciccone E, Moretta A, Moretta L . Alloantigen recognition by two human natural killer cell clones is associated with HLA-C or a closely linked gene. Proc Natl Acad Sci U S A. 1992; 89(17):7983-5. PMC: 49839. DOI: 10.1073/pnas.89.17.7983. View

17.

Colonna M, Borsellino G, Falco M, Ferrara G, Strominger J . HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells. Proc Natl Acad Sci U S A. 1993; 90(24):12000-4. PMC: 48113. DOI: 10.1073/pnas.90.24.12000. View

18.

Deniz G, Christmas S, Brew R, Johnson P . Phenotypic and functional cellular differences between human CD3- decidual and peripheral blood leukocytes. J Immunol. 1994; 152(9):4255-61. View

19.

Chumbley G, King A, Robertson K, Holmes N, Loke Y . Resistance of HLA-G and HLA-A2 transfectants to lysis by decidual NK cells. Cell Immunol. 1994; 155(2):312-22. DOI: 10.1006/cimm.1994.1125. View

20.

Kirszenbaum M, Moreau P, Gluckman E, Dausset J, Carosella E . An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes. Proc Natl Acad Sci U S A. 1994; 91(10):4209-13. PMC: 43754. DOI: 10.1073/pnas.91.10.4209. View