T cell competition for the antigen-presenting cell as a model for immunodominance in the cytotoxic T lymphocyte response against minor histocompatibility antigens.
We recently demonstrated that spleen cells primed against dominant BALB.B antigens can inhibit the cytotoxic T lymphocyte (CTL) response against subdominant antigens in vitro. In this study, we show that this interference is dependent on CD8+, but not CD4+, T cells directed against dominant antigens. Similar to immunodominance in vivo, T cell interference in vitro required presentation of dominant and subdominant antigens by the same antigen-presenting cell. In vivo priming with cells expressing dominant and subdominant antigens did not induce long-lasting unresponsiveness against the latter. These results support a model in which immunodominance is mediated by T cell competition. In line with this, we found that the immunodominance effects in the CTL response against these minor histocompatibility antigens could be broken by immunization with live bone marrow-derived dendritic cells.
Grufman
P
P
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. Per.Grufman@mtc.ki.se
Wolpert
E Z
EZ
Sandberg
J K
JK
Kärre
K
K
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D007114:Immunization; D016056:Immunodominant Epitopes; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016056:Immunodominant Epitopes; D015778:Minor Histocompatibility Antigens