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-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.
Klyushnenkova
Elena N
EN
Division of Urology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. eklyushnenkova@smail.umaryland.edu
Kouiavskaia
Diana V
DV
Berard
Carla A
CA
Alexander
Richard B
RB
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000483:Alleles; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016827:CD8 Antigens / Q000096:biosynthesis / Q000276:immunology; D045744:Cell Line, Tumor; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D015802:HLA-DR2 Antigen / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D000912:Antibodies, Neoplasm; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D017430:Prostate-Specific Antigen