Induction and functional characterization of β2-microglobulin (β2-μ)-free HLA class I heavy chains expressed by β2-μ-deficient human FO-1 melanoma cells

Zhigang Wang, Flavio Arienti, Giorgio Parmiani, Soldano Ferrone

Research output: Contribution to journalArticle

Abstract

The frequent loss of β2-microglobulin (β2-μ) in malignant cells has stimulated interest in the functional characteristics of β2-μ-free HLA class I heavy chains, since this information contributes to assess the impact of β2-μ abnormalities on the interaction of malignant cells with immune cells. Therefore, the present study has investigated the ability of β2-μ-free HLA class I heavy chains to modulate NK cell-mediated lysis of melanoma cells and to present melanoma-associated antigen (MAA)-derived peptides to HLA class I-restricted, MAA-specific cytotoxic T lymphocytes (CTL). β2-μ-free HLA class I heavy chains were induced on B2m null FO-1 cells by sequential incubation with IFN-α for 48 h at 37°C and for 24 h at 26°C. Transfection of cells with a wild-type H-2L(d) gene (FO-1L(d)) enhanced the induction of β2-μ-free HLA class I heavy chains under such experimental conditions. β2-μ-free HLA class I heavy chains expressed on the cell membrane did not protect the B2m null FO-1 cells from NK cell-mediated lysis. Furthermore, FO-1 cells which express β2-μ-free HLA-A2 heavy chains following transfection with a wild-type HLA-A2 gene were not lysed by HLA-A2-restricted, MAA-specific CTL lines and clones. These results indicate that association with β2-μ is required for interaction of HLA class I molecules with NK inhibitory receptors and for peptide presentation to CTL.

Original languageEnglish
Pages (from-to)2817-2826
Number of pages10
JournalEuropean Journal of Immunology
Volume28
Issue number9
DOIs
Publication statusPublished - Sep 1998

Keywords

  • β2-microglobulin
  • Cytotoxic T lymphocyte
  • HLA class I heavy chains
  • Melanoma
  • NK lysis

ASJC Scopus subject areas

  • Immunology

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