TCR vaccines against a murine T cell lymphoma: a primary role for antibodies of the IgG2c class in tumor protection

J Immunol. 2004 Jan 15;172(2):929-36. doi: 10.4049/jimmunol.172.2.929.


Tumor-associated proteins can act as effective immunotherapeutic targets. Immunization with tumor TCR protein conjugated to the immunogenic protein keyhole limpet hemocyanin (KLH) protects mice from tumor challenge with the murine T cell lymphoma C6VL. The immune mechanisms responsible for this tumor protection are of interest for designing more effective vaccine strategies. Previous studies using depletion experiments had suggested a CD8-mediated component of protection induced by TCR-KLH vaccines. In this study we used CD8alpha knockout, micro MT, and FcgammaR knockout mice to investigate the relative roles of CD8+ T cells and Ab in protective immunity induced by TCR-KLH immunization. We found that CD8+ T cells are not required for tumor protection, although they may contribute to protection. Vaccine-induced Abs are sufficient to mediate protection against this murine T cell lymphoma through an FcR-dependent mechanism. This was confirmed with Ab transfers, which protect challenged mice. Additionally, recombinase-activating gene 1(-/-) splenocytes can mediate Ab-dependent cellular cytotoxicity against this tumor in the presence of bound anti-TCR Abs. IFN-gamma knockout mice demonstrated a requirement for IFN-gamma, probably via generation of IgG2c Abs, in vaccine-induced tumor protection. IFN-gamma knockout mice were not protected by immunization and had a severe impairment in IgG2c Ab production in response to immunization. Although mock-depleted anti-TCR Abs could transfer tumor protection, IgG2c-deficient anti-TCR Abs were unable to transfer tumor protection to wild-type mice. These results suggest that TCR-KLH vaccine-induced tumor protection in the C6VL system is primarily attributable to the induction of IgG2c Abs and humoral immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Neoplasm / biosynthesis
  • Antibodies, Neoplasm / physiology*
  • Antibody-Dependent Cell Cytotoxicity / genetics
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Female
  • Hemocyanins / administration & dosage
  • Hemocyanins / immunology
  • Immunization, Passive
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / physiology*
  • Immunoglobulin Isotypes / biosynthesis
  • Immunoglobulin Isotypes / physiology*
  • Interferon-gamma / physiology
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / immunology
  • Lymphoma, T-Cell / immunology*
  • Lymphoma, T-Cell / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, alpha-beta / administration & dosage
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Fc / physiology
  • T-Lymphocytes, Cytotoxic / immunology


  • Adjuvants, Immunologic
  • Antibodies, Neoplasm
  • Cancer Vaccines
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Fc
  • Interleukin-12
  • Interferon-gamma
  • Hemocyanins
  • keyhole-limpet hemocyanin