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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Aug 1;180(2):537–543. doi: 10.1084/jem.180.2.537

NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules

PMCID: PMC2191610  PMID: 8046332

Abstract

Natural killer (NK) cells kill normal and transformed hematopoietic cells that lack expression of major histocompatibility complex (MHC) class I antigens. Lysis of HLA-negative Epstein Barr virus-transformed B lymphoblastoid cell lines (B-LCL) by human NK cell clones can be inhibited by transfection of the target cells with certain HLA-A, -B, or -C alleles. NK cell clones established from an individual demonstrate clonal heterogeneity in HLA recognition and a single NK clone can recognize multiple alleles. We describe a potential human NK cell receptor (NKB1) for certain HLA-B alleles (e.g., HLA-B*5101 and- B*5801) identified by the mAb DX9. NKB1 is a 70-kD glycoprotein that is expressed on a subset of NK cells and NK cell clones. DX9 monoclonal antibody (mAb) specifically inhibits the interaction between NK cell clones and B-LCL targets transfected with certain HLA-B alleles, but does not affect recognition of HLA-A or HLA-C antigens. An individual NK cell clone can independently recognize B-LCL targets transfected with HLA-B or HLA-C antigens; however, DX9 mAb only affects interaction with transfectants expressing certain HLA-B alleles. These findings demonstrate the existence of NK cell receptors involved in the recognition of HLA-B and imply the presence of multiple receptors for MHC on an individual NK clone.

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Selected References

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  1. Ciccone E., Pende D., Viale O., Than A., Di Donato C., Orengo A. M., Biassoni R., Verdiani S., Amoroso A., Moretta A. Involvement of HLA class I alleles in natural killer (NK) cell-specific functions: expression of HLA-Cw3 confers selective protection from lysis by alloreactive NK clones displaying a defined specificity (specificity 2). J Exp Med. 1992 Oct 1;176(4):963–971. doi: 10.1084/jem.176.4.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Colonna M., Borsellino G., Falco M., Ferrara G. B., Strominger J. L. 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 Dec 15;90(24):12000–12004. doi: 10.1073/pnas.90.24.12000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Colonna M., Brooks E. G., Falco M., Ferrara G. B., Strominger J. L. Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. Science. 1993 May 21;260(5111):1121–1124. doi: 10.1126/science.8493555. [DOI] [PubMed] [Google Scholar]
  4. Colonna M., Spies T., Strominger J. L., Ciccone E., Moretta A., Moretta L., Pende D., Viale O. 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 Sep 1;89(17):7983–7985. doi: 10.1073/pnas.89.17.7983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Edwards P. A., Smith C. M., Neville A. M., O'Hare M. J. A human-hybridoma system based on a fast-growing mutant of the ARH-77 plasma cell leukemia-derived line. Eur J Immunol. 1982 Aug;12(8):641–648. doi: 10.1002/eji.1830120804. [DOI] [PubMed] [Google Scholar]
  6. Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
  7. Lanier L. L., Buck D. W., Rhodes L., Ding A., Evans E., Barney C., Phillips J. H. Interleukin 2 activation of natural killer cells rapidly induces the expression and phosphorylation of the Leu-23 activation antigen. J Exp Med. 1988 May 1;167(5):1572–1585. doi: 10.1084/jem.167.5.1572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lanier L. L., Le A. M., Phillips J. H., Warner N. L., Babcock G. F. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol. 1983 Oct;131(4):1789–1796. [PubMed] [Google Scholar]
  9. Litwin V., Gumperz J., Parham P., Phillips J. H., Lanier L. L. Specificity of HLA class I antigen recognition by human NK clones: evidence for clonal heterogeneity, protection by self and non-self alleles, and influence of the target cell type. J Exp Med. 1993 Oct 1;178(4):1321–1336. doi: 10.1084/jem.178.4.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ljunggren H. G., Kärre K. Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J Exp Med. 1985 Dec 1;162(6):1745–1759. doi: 10.1084/jem.162.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moretta A., Bottino C., Pende D., Tripodi G., Tambussi G., Viale O., Orengo A., Barbaresi M., Merli A., Ciccone E. Identification of four subsets of human CD3-CD16+ natural killer (NK) cells by the expression of clonally distributed functional surface molecules: correlation between subset assignment of NK clones and ability to mediate specific alloantigen recognition. J Exp Med. 1990 Dec 1;172(6):1589–1598. doi: 10.1084/jem.172.6.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sentman C. L., Hackett J., Jr, Kumar V., Bennett M. Identification of a subset of murine natural killer cells that mediates rejection of Hh-1d but not Hh-1b bone marrow grafts. J Exp Med. 1989 Jul 1;170(1):191–202. doi: 10.1084/jem.170.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shimizu Y., DeMars R. Demonstration by class I gene transfer that reduced susceptibility of human cells to natural killer cell-mediated lysis is inversely correlated with HLA class I antigen expression. Eur J Immunol. 1989 Mar;19(3):447–451. doi: 10.1002/eji.1830190306. [DOI] [PubMed] [Google Scholar]
  14. Shimizu Y., DeMars R. Production of human cells expressing individual transferred HLA-A,-B,-C genes using an HLA-A,-B,-C null human cell line. J Immunol. 1989 May 1;142(9):3320–3328. [PubMed] [Google Scholar]
  15. Storkus W. J., Alexander J., Payne J. A., Dawson J. R., Cresswell P. Reversal of natural killing susceptibility in target cells expressing transfected class I HLA genes. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2361–2364. doi: 10.1073/pnas.86.7.2361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376. doi: 10.1016/S0065-2776(08)60664-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wong S., Freeman J. D., Kelleher C., Mager D., Takei F. Ly-49 multigene family. New members of a superfamily of type II membrane proteins with lectin-like domains. J Immunol. 1991 Aug 15;147(4):1417–1423. [PubMed] [Google Scholar]
  18. Yokoyama W. M., Kehn P. J., Cohen D. I., Shevach E. M. Chromosomal location of the Ly-49 (A1, YE1/48) multigene family. Genetic association with the NK 1.1 antigen. J Immunol. 1990 Oct 1;145(7):2353–2358. [PubMed] [Google Scholar]
  19. Yssel H., De Vries J. E., Koken M., Van Blitterswijk W., Spits H. Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J Immunol Methods. 1984 Aug 3;72(1):219–227. doi: 10.1016/0022-1759(84)90450-2. [DOI] [PubMed] [Google Scholar]
  20. Zemmour J., Little A. M., Schendel D. J., Parham P. The HLA-A,B "negative" mutant cell line C1R expresses a novel HLA-B35 allele, which also has a point mutation in the translation initiation codon. J Immunol. 1992 Mar 15;148(6):1941–1948. [PubMed] [Google Scholar]

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