Anti-class II antibodies, but not cytotoxic T-lymphocyte antigen 4-immunoglobulin hybrid molecules, prevent rejection of major histocompatibility complex class II-negative myeloma in T-cell receptor-transgenic mice.
We have previously shown that tumour-specific CD4+ T cells protect against subcutaneous injections of major histocompatibility complex (MHC) class II-negative MOPC315 myeloma cells. Here, we have interfered with the immunologic events that lead to successful rejection of MOPC315 challenges in T-cell receptor (TCR)-transgenic mice. The CD4+ T cells have a transgene-encoded TCR specific for a MOPC315 V-region idiotypic (Id) peptide presented on the MHC class II molecule E(d). A side-by-side comparison indicated that DNA-recombination-deficient TCR-transgenic mice were better protected against MOPC315 tumour development than recombination-sufficient counterparts, suggesting that B cells or endogenous TCR chains might facilitate tumour progression in this model. Intraperitoneal injections of E(d)-specific antibodies over a period of initial 24 days, abrogated protection against tumours in both strains of mice. By contrast, injections of anticostimulatory molecules (cytotoxic T-lymphocyte antigen 4-immunoglobulin hybrid molecules) had no effect. The findings demonstrate that tumour rejection depends on the presence of MHC class II molecules, despite the fact that MOPC315 tumour cells themselves do not express them. The results are consistent with the idea that secreted myeloma protein is processed and presented by class II+ antigen-presenting cells to Id-specific naïve CD4+ T cells that become activated and kill the myeloma cells by a bystander mechanism. While Id presentation on class II molecules is absolutely required for tumour rejection, costimulatory CD80/CD86 molecules might be dispensible in this process.
Dembic
Z
Z
Institute of Immunology, University of Oslo, PB 1052 Blindern, N-0316 Oslo, Norway. zlatko.dembic@labmed.uoi.no
Hofgaard
P O
PO
Omholt
H
H
Bogen
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000494:pharmacology; D060908:CTLA-4 Antigen; D002455:Cell Division / Q000276:immunology; D003433:Crosses, Genetic; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D010954:Plasmacytoma / Q000276:immunology* / Q000517:prevention & control; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes; D011948:Receptors, Antigen, T-Cell