Cutting Edge: Permissive MHC Class II Allele Changes the Pattern of Antitumor Immune Response Resulting in Failure of Tumor Rejection

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-Ab-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.