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. 2001 Nov;85(10):1527–1534. doi: 10.1054/bjoc.2001.2089

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

R Sotiriadou 1, S A Perez 1, A D Gritzapis 1, P A Sotiropoulou 1, H Echner 2, S Heinzel 3,4, A Mamalaki 5, G Pawelec 3, W Voelter 2, C N Baxevanis 1, M Papamichail 1
PMCID: PMC2363935  PMID: 11720440

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)-γ] 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 TCRVbeta6.7+ 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.© 2001 Cancer Research Campaign  http://www.bjcancer.com

Keywords: HER-2/neu peptide, CD4+ T cell clones, MHC alleles, vaccines, cancer immunotherapy

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Selected References

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