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Peptide HER2(776-788) represents a naturally processed broad MHC class II-restricted T cell epitope.

Abstract
HER2/neu-derived peptides inducing MHC class II-restricted CD4+ T helper lymphocyte (Th) responses, although critical for tumour rejection, are not thoroughly characterized. Here, we report the generation and characterization of CD4+ T cell clones specifically recognizing a HER-2/neu-derived peptide (776-788) [designated HER2(776-788)]. Such clones yielded specific proliferative and cytokine [gamma-interferon(IFN)-gamma] responses when challenged with autologous dendritic cells (DCs) loaded with HER2(776-788). By performing blocking studies with monoclonal antibodies (MAbs) and by using DCs from allogeneic donors sharing certain HLA-DR alleles, we found that HER2(776-788) is a promiscuous peptide presented, at least, by DRB5*0101, DRB1*0701 and DRB1*0405 alleles. One TCRV beta 6.7+ clone recognized the HLA-DRB5*0101+ FM3 melanoma cell line transfected with a full length HER-2/neu cDNA. Moreover, this clone recognized the HER-2/neu+ SKBR3 breast cancer cell line induced to express HLA-DR, thus demonstrating that HER2(776-788) represents a naturally processed and presented epitope. Our data demonstrate that helper peptide HER2(776-788) represents a promiscuous epitope binding to at least three HLA-DR alleles, thus offering a broad population coverage. The use of antigenic peptides presented by major histocompatibility complex (MHC) class II in addition to those presented by class I may improve the therapeutic efficacy of active immunization.
AuthorsR Sotiriadou, S A Perez, A D Gritzapis, P A Sotiropoulou, H Echner, S Heinzel, A Mamalaki, G Pawelec, W Voelter, C N Baxevanis, M Papamichail
JournalBritish journal of cancer (Br J Cancer) Vol. 85 Issue 10 Pg. 1527-34 (Nov 16 2001) ISSN: 0007-0920 [Print] Scotland
PMID11720440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HER2(776-788)
  • HLA-DR Antigens
  • Peptide Fragments
  • Peptides
  • Interferon-gamma
  • Receptor, ErbB-2
Topics
  • Antigen Presentation
  • Antigens, Neoplasm (immunology)
  • Cell Line
  • Cells, Cultured
  • Clone Cells
  • Epitopes, T-Lymphocyte (immunology)
  • HLA-DR Antigens (physiology)
  • Humans
  • Interferon-gamma (biosynthesis)
  • Lymphocyte Activation
  • Neoplasms (immunology)
  • Peptide Fragments (immunology)
  • Peptides (immunology)
  • Receptor, ErbB-2 (immunology)
  • T-Lymphocytes, Cytotoxic (immunology)
  • Tumor Cells, Cultured

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