Independent contributions of HLA epitopes and killer inhibitory receptor expression to the functional alloreactive specificity of natural killer cells

Neil Thomas Young, N A Rust, M J Dallman, V Cerundolo, P J Morris, K I Welsh

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Human NK cells express receptors (KIR) which inhibit lysis through binding to HLA class I on target cells. KIR expression in different individuals has not been intensively investigated and it is not known how the KIR repertoire relates to HLA type or influences the overall activity of NK populations. This may be important in the response of NK cells to HLA-mismatched organ transplants since the ligands for KIR are supertypic epitopes shared between certain HLA alleles. We studied the effect of matching for HLA on the cytotoxicity of NK cells from individuals homozygous or heterozygous for relevant HLA class I epitopes and correlated this with KIR expression and genotype. Considerable variation in the KIR repertoire of different donors was evident, including functional KIR expressed in the absence of specific HLA ligands. We confirmed the predominant influence of HLA-C in a hierarchy of inhibitory effects mediated by HLA class I loci. In certain individuals, inhibition patterns are more complicated and may be due to the relative expression of the CD94/NKG2 receptors. Our study reveals the separate contributions of HLA and KIR molecules to NK cell alloreactivity and provides a basis for consideration of the functional diversity of KIR genes in transplantation.
Original languageEnglish
Pages (from-to)700-712
Number of pages13
JournalHuman Immunology
Volume59
Issue number11
DOIs
Publication statusPublished - 1 Nov 1998

Keywords

  • ATP-Binding Cassette Transporters
  • Antibodies, Monoclonal
  • Antigens, CD
  • Cell Line
  • Cytotoxicity, Immunologic
  • Epitopes
  • Flow Cytometry
  • Genotype
  • HLA Antigens
  • HLA-D Antigens
  • Histocompatibility Antigens Class I
  • Humans
  • Isoantigens
  • Killer Cells, Natural
  • Lectins
  • Lectins, C-Type
  • Leukocytes, Mononuclear
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic
  • Receptors, KIR
  • Tumor Cells, Cultured

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