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. 1996 Feb 1;183(2):645–650. doi: 10.1084/jem.183.2.645

The human leukocyte antigen (HLA)-C-specific "activatory" or "inhibitory" natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions

PMCID: PMC2192451  PMID: 8627176

Abstract

Natural killer cells express clonally distributed receptors specific for major histocompatibility complex class I molecules. The human leukocyte antigen (HLA)-C-specific receptors have been molecularly identified and cloned. They exist not only as inhibitory (p58) but also as activatory (p50) receptors. Here we show that p50 and p58 are highly homologous in their extracellular regions formed by two Ig-like domains. In contrast, major differences exist in their transmembrane and cytoplasmic portions. Whereas p 58 displays a 76-84-amino acid cytoplasmic tail containing an unusual antigen receptor activation motif, p50 is characterized by a shorter 39-amino acid tail. In addition, whereas p58 has a nonpolar transmembrane portion, p50 contains the charged amino acid Lys. These data strongly suggest that receptors with identical HLA-C allele specificity can mediate functions of opposite sign owing to their different transmembrane/cytoplasmic portions.

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Selected References

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  1. Bennett M., Yu Y. Y., Stoneman E., Rembecki R. M., Mathew P. A., Lindahl K. F., Kumar V. Hybrid resistance: 'negative' and 'positive' signaling of murine natural killer cells. Semin Immunol. 1995 Apr;7(2):121–127. doi: 10.1006/smim.1995.0016. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Litwin V., Gumperz J., Parham P., Phillips J. H., Lanier L. L. NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules. J Exp Med. 1994 Aug 1;180(2):537–543. doi: 10.1084/jem.180.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Long E. O., Rosen-Bronson S., Karp D. R., Malnati M., Sekaly R. P., Jaraquemada D. Efficient cDNA expression vectors for stable and transient expression of HLA-DR in transfected fibroblast and lymphoid cells. Hum Immunol. 1991 Aug;31(4):229–235. doi: 10.1016/0198-8859(91)90092-n. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Moretta A., Sivori S., Vitale M., Pende D., Morelli L., Augugliaro R., Bottino C., Moretta L. Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells. J Exp Med. 1995 Sep 1;182(3):875–884. doi: 10.1084/jem.182.3.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Moretta A., Tambussi G., Bottino C., Tripodi G., Merli A., Ciccone E., Pantaleo G., Moretta L. A novel surface antigen expressed by a subset of human CD3- CD16+ natural killer cells. Role in cell activation and regulation of cytolytic function. J Exp Med. 1990 Mar 1;171(3):695–714. doi: 10.1084/jem.171.3.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Moretta A., Vitale M., Bottino C., Orengo A. M., Morelli L., Augugliaro R., Barbaresi M., Ciccone E., Moretta L. P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J Exp Med. 1993 Aug 1;178(2):597–604. doi: 10.1084/jem.178.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moretta A., Vitale M., Sivori S., Bottino C., Morelli L., Augugliaro R., Barbaresi M., Pende D., Ciccone E., Lopez-Botet M. Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles. J Exp Med. 1994 Aug 1;180(2):545–555. doi: 10.1084/jem.180.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Naper C., Vaage J. T., Lambracht D., Løvik G., Butcher G. W., Wonigeit K., Rolstad B. Alloreactive natural killer cells in the rat: complex genetics of major histocompatibility complex control. Eur J Immunol. 1995 May;25(5):1249–1256. doi: 10.1002/eji.1830250518. [DOI] [PubMed] [Google Scholar]
  13. Pérez-Villar J. J., Melero I., Rodríguez A., Carretero M., Aramburu J., Sivori S., Orengo A. M., Moretta A., López-Botet M. Functional ambivalence of the Kp43 (CD94) NK cell-associated surface antigen. J Immunol. 1995 Jun 1;154(11):5779–5788. [PubMed] [Google Scholar]
  14. Wagtmann N., Biassoni R., Cantoni C., Verdiani S., Malnati M. S., Vitale M., Bottino C., Moretta L., Moretta A., Long E. O. Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity. 1995 May;2(5):439–449. doi: 10.1016/1074-7613(95)90025-x. [DOI] [PubMed] [Google Scholar]
  15. Weiss A., Littman D. R. Signal transduction by lymphocyte antigen receptors. Cell. 1994 Jan 28;76(2):263–274. doi: 10.1016/0092-8674(94)90334-4. [DOI] [PubMed] [Google Scholar]

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