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Cutting Edge: Permissive MHC Class II Allele Changes the Pattern of Antitumor Immune Response Resulting in Failure of Tumor Rejection¹

Elena N. Klyushnenkova^2,*,, Diana V. Kouiavskaia^*, Carla A. Berard and Richard B. Alexander^*,,

^* Division of Urology, University of Maryland School of Medicine and University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201; and Section of Urology, Veterans Affairs Maryland Health Care System, Baltimore, MD 21201

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant DK65268, an Intramural Pilot Grant from the University of Maryland Greenebaum Cancer Center, American Cancer Society Institutional Research Grant 97-153-04, and by a grant from the U.S. Department of Veterans Affairs.

² Address correspondence and reprint requests to Dr. Elena N. Klyushnenkova, Department of Surgery/Urology, University of Maryland School of Medicine, 10 South Pine Street, Medical School Teaching Facility 4-00A, Baltimore MD 21201. E-mail address: eklyushnenkova{at}smail.umaryland.edu

³ Abbreviations used in this paper: PSA, prostate-specific antigen; TRAMP, transgenic adenocarcinoma of mouse prostate.

⁴ The online version of this article contains supplemental material.