HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells

M. Colonna, G. Borsellino, M. Falco, G. B. Ferrara, J. L. Strominger

Research output: Contribution to journalArticle

379 Scopus citations

Abstract

Natural killer (NK) cells recognize alloantigens on normal cells. One of these alloantigens correlates with homozygosity for a dimorphism of HLA-C at positions 77-80, which is shared by a number of HLA-C alleles. A second allelic alloantigen correlates with homozygosity for the alternative HLA-C dimorphism, which is shared by the remaining HLA-C alleles. Moreover, NK1- and NK2-specific NK cell lines can be generated by mixed leukocyte cultures in which donor and stimulator are homozygous for the alternative dimorphisms at positions 77-80 of HLA-C. In the present work, the role of HLA-C in NK cell-mediated allorecognition was directly investigated by analyzing the effects produced by transfection of several HLA-C alleles on NK sensitivity of class I-deleted mutant cell lines. Transfection of cells with HLA-C alleles encoding Asn-77-Lys-80 (including HLA-Cw4, -Cw5, and -Cw6) inhibited the lysis of the targets by NK1-specific NK cells, whereas HLA-C alleles encoding Ser-77-Asn-80 (including HLA-Cw1, -Cw7, and -Cw13) protected the targets from NK2-specific NK cells. Thus, HLA-C alleles are the dominant inhibitory ligands that protect targets from lysis by these allospecific NK cells.

Original languageEnglish
Pages (from-to)12000-12004
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number24
DOIs
StatePublished - Dec 29 1993
Externally publishedYes

Keywords

  • allorecognition
  • cytotoxicity
  • dimorphism
  • major histocompatibility complex

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