Role of SEREX-defined immunogenic wild-type cellular molecules in the development of tumor-specific immunity Journal Article


Authors: Nishikawa, H.; Tanida, K.; Ikeda, H.; Sakakura, M.; Miyahara, Y.; Aota, T.; Mukai, K.; Watanabe, M.; Kuribayashi, K.; Old, L. J.; Shiku, H.
Article Title: Role of SEREX-defined immunogenic wild-type cellular molecules in the development of tumor-specific immunity
Abstract: Recognition of altered self-antigens in tumor cells by lymphocytes forms the basis for antitumor immune responses. The effector cells in most experimental tumor systems are CD8+ T cells that recognize MHC class I binding peptides derived from molecules with altered expression in tumor cells. Although the need for CD4+ helper T cells in regulating CD8+ T cells has been documented, their target epitopes and functional impact in antitumor responses remain unclear. We examined whether broadly expressed wild-type molecules in murine tumor cells eliciting humoral immunity contributed to the generation of CD8+ T cells and protective antitumor immune responses to unrelated tumor-specific antigens [mutated ERK2 (mERK2) and c-erbB2/HER/neu (HER2)]. The immunogenic wild-type molecules, presumably dependent on recognition by CD4+ helper T cells, were defined by serological analysis of recombinant cDNA expression libraries (SEREX) using tumor-derived λ phage libraries screened with IgG antibodies of hosts bearing transplanted 3-methylchoranthrene-induced tumors. Coimmunization of mice with plasmids encoding SEREX-defined murine wild-type molecules and mERK2 or HER2 led to a profound increase in CD8+ T cells specific for mERK2 or HER2 peptides. This heightened response depended on CD4+ T cells and copresentation of SEREX-defined molecules and CD8+ T cell epitopes. In tumor protection assays, immunization with SEREX-defined wild-type molecules and mERK2 resulted in an inhibition of pulmonary metastasis, which was not achieved by immunization with mERK2 alone.
Keywords: mitogen activated protein kinase; controlled study; mutation; nonhuman; t lymphocyte; cd8-positive t-lymphocytes; animal cell; animals; mice; animal tissue; gene expression; lung neoplasms; animal experiment; animal model; tumor cells, cultured; tumor antigen; mice, inbred balb c; lung metastasis; antigens, neoplasm; antigen recognition; cd4-positive t-lymphocytes; neoplasms, experimental; autoantigens; tumor immunity; receptor, erbb-2; immunostimulation; antigen binding; humoral immunity; complementary dna; lymphocyte function; helper cell; immunization; oncogene neu; epitopes; mitogen-activated protein kinase 1; female; priority journal; article; oncogene c erb
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 98
Issue: 25
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2001-12-04
Start Page: 14571
End Page: 14576
Language: English
DOI: 10.1073/pnas.251547298
PUBMED: 11724951
PROVIDER: scopus
PMCID: PMC64723
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
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  1. Lloyd J Old
    549 Old