Cutting edge: permissive MHC class II allele changes the pattern of antitumor immune response resulting in failure of tumor rejection

J Immunol. 2009 Feb 1;182(3):1242-6. doi: 10.4049/jimmunol.182.3.1242.

Abstract

We studied the growth of transgenic adenocarcinoma of mouse prostate (TRAMP)-C1 tumor cells expressing human prostate-specific Ag (PSA) in HLA-DRB1*1501 (DR2b) transgenic mice. TRAMP-PSA tumors were frequently rejected by HLA-DR2b(-) mice but had increased incidence in HLA-DR2b(+) littermates. The levels of PSA-specific CD8 T cell responses were significantly higher in the HLA-DR2b(-) mice that rejected TRAMP-PSA tumors compared with HLA-DR2b(+) tumor-bearing littermates. In contrast, Ab responses to PSA were strong in HLA-DR2b(+) mice bearing TRAMP-PSA tumors and were virtually undetectable in HLA-DR2b(-) littermates. The analysis of CD4 T cell responses to PSA revealed the presence of several CD4 T cell epitopes in HLA-DR2b(+) mice but failed to identify strong I-A(b)-restricted epitopes in HLA-DR2b(-) mice. Our data demonstrate that the expression of a permissive HLA class II allele can change the pattern of the immune response to a tumor Ag, resulting in the failure of tumor rejection.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Alleles*
  • Animals
  • Antibodies, Neoplasm / biosynthesis
  • Antibodies, Neoplasm / physiology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8 Antigens / biosynthesis
  • CD8 Antigens / immunology
  • Cell Line, Tumor
  • Graft Rejection / genetics
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Graft Survival / genetics
  • Graft Survival / immunology*
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / immunology
  • HLA-DR2 Antigen / genetics*
  • HLA-DR2 Antigen / immunology
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Incidence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Prostate-Specific Antigen / biosynthesis
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / immunology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology

Substances

  • Antibodies, Neoplasm
  • CD8 Antigens
  • HLA-DR Antigens
  • HLA-DR2 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*15:01 antigen
  • Histocompatibility Antigens Class II
  • I-A(b) antigen, mouse
  • Prostate-Specific Antigen