Tumorigenicity and immunogenicity of murine tumor cells expressing an MHC class II molecule with a covalently bound antigenic peptide

Andrea Ladányi, Michael I. Nishimura, Steven A. Rosenberg, James C. Yang

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Abstract

The significance of CD4+ lymphocytes and major histocompatibility complex (MHC) class II-restricted antigens in antitumor immunity has been demonstrated in several animal models as well as in some human tumors. However, because of the lack of known class II-restricted antigens, the participation of CD4+ cells in antitumor responses has not been well characterized. Recent reports showed that class II proteins covalently linked to an antigenic peptide could be constructed and cells expressing these fusion proteins were recognized by specific T(H) cells. The aim of this study was to determine the effect of the expression of a class II-peptide construct on the tumorigenicity and immunogenicity of transfected murine tumor cells. We have constructed a gene for I-E(d) β chain covalently coupled to the I- E(d)-restricted T(H) cell determinant of sperm whale myoglobin (SWM132- 145). This class II fusion protein was recognized by a specific T(H) cell line on the surface of COS-7 cells or BALB/c sarcoma cells. The sarcoma cells expressing the MHC-peptide complex were rejected by immunocompetent BALB/c mice, and in vivo T-cell subset depletion experiments suggested the importance of CD4+ cells in the rejection. Moreover, splenocytes from mice immunized with tumor cells expressing the I-E(d)-SWM complex showed specific peptide recognition in vitro. Such covalent MHC-peptide complexes could prove useful in studies on the role of CD4+ lymphocytes in antitumor immune responses, and also in designing new, more effective vaccine approaches to the immunotherapy of cancer, as class II-restricted tumor-associated antigens are identified for human cancers.

Original languageEnglish
Pages (from-to)36-47
Number of pages12
JournalJournal of Immunotherapy
Volume23
Issue number1
DOIs
Publication statusPublished - Feb 15 2000

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Keywords

  • CD4 lymphocytes
  • MHC class II
  • Tumor antigens
  • Vaccination

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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