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

Bibliographic Details
Title: Peptide HER2(776–788) represents a naturally processed broad MHC class II-restricted T cell epitope
Authors: Avgi Mamalaki, Constantin N. Baxevanis, Michael Papamichail, Sonia A. Perez, Graham Pawelec, Panagiota A. Sotiropoulou, R Sotiriadou, Hartmut Echner, Susanne Heinzel, Wolfgang Voelter, Angelos D. Gritzapis
Source: British Journal of Cancer
British Journal of Cancer, 85 (10
Publisher Information: Springer Science and Business Media LLC, 2001.
Publication Year: 2001
Subject Terms: Cancer Research, Oncology, MHC class I, biology.protein, biology, Antigen presentation, T cell, medicine.anatomical_structure, medicine, Antigen, Major histocompatibility complex, Epitope, Cytotoxic T cell, MHC class II, Virology, skin and connective tissue diseases, Regular Article, HER-2/neu peptide, CD4+ T cell clones, MHC alleles, vaccines, cancer immunotherapy, Sciences bio-médicales et agricoles, 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
Description: 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.
Journal Article
Research Support, Non-U.S. Gov't
File Description: 1 full-text file(s): application/pdf
ISSN: 1532-1827
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Rights: OPEN
Accession Number: edsair.doi.dedup.....b5c064cbd2aea380c07af5715e2ac6a1
Database: OpenAIRE