Ii-Key/HER-2/neu(776-790) hybrid peptides induce more effective immunological responses over the native peptide in lymphocyte cultures from patients with HER-2/neu+ tumors

Cancer Immunol Immunother. 2007 May;56(5):601-13. doi: 10.1007/s00262-006-0213-z. Epub 2006 Sep 8.


We have demonstrated that coupling an immunoregulatory segment of the MHC class II-associated invariant chain (Ii), the Ii-Key peptide, to a promiscuous MHC class II epitope significantly enhances its presentation to CD4+ T cells. Here, a series of homologous Ii-Key/HER-2/neu(776-790) hybrid peptides, varying systematically in the length of the epitope(s)-containing segment, are significantly more potent than the native peptide in assays using T cells from patients with various types of tumors overexpressing HER-2/neu. In particular, priming normal donor and patient PBMCs with Ii-Key hybrid peptides enhances recognition of the native peptide either pulsed onto autologous dendritic cells (DCs) or naturally presented by IFN-gamma-treated autologous tumor cells. Moreover, patient-derived CD4+ T cells primed with the hybrid peptides provide a significantly stronger helper effect to autologous CD8+ T cells specific for the HER-2/neu(435-443) CTL epitope, as illustrated by either IFN-gamma ELISPOT assays or specific autologous tumor cell lysis. Hybrid peptide-specific CD4+ T cells strongly enhanced the antitumor efficacy of HER-2/neu(435-443) peptide-specific CTL in the therapy of xenografted SCID mice inoculated with HER-2/neu overexpressing human tumor cell lines. Our data indicate that the promiscuously presented vaccine peptide HER-2/neu(776-790) is amenable to Ii-Key-enhancing effects and supports the therapeutic potential of vaccinating patients with HER-2/neu+ tumors with such Ii-Key/HER-2/neu(776-790) hybrid peptides.

MeSH terms

  • Antigen Presentation / immunology
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Lymphocyte Activation / immunology
  • Peptide Fragments / immunology
  • Receptor, ErbB-2 / immunology*
  • Recombinant Proteins / immunology*
  • T-Lymphocyte Subsets / immunology*


  • Antigens, Differentiation, B-Lymphocyte
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Peptide Fragments
  • Recombinant Proteins
  • invariant chain
  • Receptor, ErbB-2