HER-2/neu peptide specificity in the recognition of HLA-A2 by natural killer cells

Larry D. Anderson, J. Michael Hudson, Cherylyn A. Savary, Bryan Fisk, David M. Gershenson, Constantin G. Ioannides

Research output: Contribution to journalArticle

Abstract

Although natural killer (NK) cells have been described as non-MHC- restricted, new evidence suggests that NK activity can be either up- or down- regulated after interaction with the peptide-MHC-class-I complex expressed on target cells. However, the epitope(s) recognized by NK cells have remained ill-defined. We investigated NK cell recognition of synthetic peptides representing a portion of a self-protein encoded by the HER-2/neu (HER-2) proto-oncogene and presented by HLA-A2. HER-2 nonapeptides C85, E89, and E75 were found partially to protect T2 targets from lysis by freshly isolated and interleukin-2(IL-2)-activated NK cells (either HLA-A2+ or A2-). This inhibition was not solely due to changes in the level of HLA-A2 expression or conformation of serological HLA-A2 epitopes. Using single-amino-acid variants at position 1 (P1) of two HER-2 peptides, we observed that protection of targets was dependent on the sequence and the side-chain. These results suggest similarities in the mechanism of target recognition by NK and T cells. This information may be important for understanding the mechanisms of tumor escape from immunosurveillance and could help explain the aggressiveness of HER-2-overexpressing tumor cells.

Original languageEnglish (US)
Pages (from-to)401-410
Number of pages10
JournalCancer Immunology Immunotherapy
Volume48
Issue number7
DOIs
StatePublished - Oct 12 1999

Keywords

  • HER-2/neu
  • MHC
  • Natural killer cells
  • Peptides
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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