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.

• Authors: R 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
• Journal: British journal of cancer (Br J Cancer) Vol. 85 Issue 10 Pg. 1527-34 (Nov 16 2001) ISSN: 0007-0920 [Print] England
• PMID: 11720440 (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