General role of HLA class I molecules in the protection of target cells from lysis by natural killer cells: Evidence that the free heavy chains of class I molecules are not sufficient to mediate the protective effect

E. Ciccone, D. Pende, L. Nanni, C. Di Donato, O. Viale, A. Beretta, M. Vitale, S. Sivori, A. Moretta, L. Moretta

Research output: Contribution to journalArticlepeer-review

Abstract

Some HLA-C alleles have been shown to exert a specific protective effect preventing target cells from lysis by groups of natural killer (NK) clones displaying a defined specificity. In this study, we analyzed whether class I-mediated protection is a more general phenomenon involving all NK cells. First, we utilized two anti-class I mAbs (6A4 of IgG1 isotype and A6-136 of IgM isotype), which had been shown to induce lysis of protected target cells by group 1 and group 2 NK clones. Addition of A6-136 or 6A4 used as F(ab') 2 mAb resulted in lysis of protected target cells by all NK clones analyzed. Target cells were represented by a panel of HLA homozygous Epstein-Barr virus-transformed B cell lines (B-EBV) while NK clones were representative of clones displaying different GL183/EB6 surface phenotypes and/or different abilities to lyse allogeneic cells. Unselected NK clones derived from seven different individuals were tested against autologous target cells represented by phytohemagglutinin-induced blasts or B-EBV transformed cell lines, in both instances, addition of a mixture of 6A4 F(ab')a and A6-136 mAbs resulted in lysis of autologous target cells, thus suggesting that class I molecules prevent lysis of normal cells by self NK cells. We further investigated whether the class I-mediated protection requires the complexed form of class I molecules (composed of a chain, β 2-microglobulin and the antigen peptide) or rather the free a chain. Acidic treatment of the C1R (Cw4 +) target cells or 81.22 (Cw3 +, Cw4 +) at pH 2.2 resulted in loss of reactivity with 6A4, A6-136 and W6-32 mAb (known to react with the assembled form of class I molecules) and in the de novo reactivity with L31 mAb (specific for the HLA-C free chain). While the untreated Cw4 + C1R cells were resistant to lysis by the Cw4-specific group 1 NK clones, the pH 2.2-treated cells became highly susceptible to lysis by the same clones. These data indicate that, at least for the NK clones analyzed, the protection of target cells requires class I molecules in the complexed form.

Original languageEnglish
Pages (from-to)393-400
Number of pages8
JournalInternational Immunology
Volume7
Issue number3
Publication statusPublished - 1995

Keywords

  • Class I
  • HLA
  • Natural killer
  • Protection

ASJC Scopus subject areas

  • Immunology

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