The immune response to cytochrome c in BALB/c mice is delayed due to inability of their non-specific antigen-presenting cells to provide its immunodominant epitope.
The antibody response to horse cytochrome c (cyt.c) in BALB/c mice developed slowly and a substantial production of IgG antibodies was observed only 26-30 days after immunization. Lymph node cells (LNC) of unimmunized mice proliferated weakly in response to both native cyt.c and its synthetic peptides. On day 8 after immunization, LNC could not be stimulated with native cyt.c and peptide 92-104. However, they did proliferate in response to cyt.c peptides 1-6, 1-13, 2-13, 14-22, 46-56, 57-77, 61-77 and 61-69 which are closely related in horse and mouse cyt.c. On day 26, both native cyt.c and the peptides, including 92-104, were equally active in stimulating LNC proliferation. Both plastic-adherent and cyt.c-specific cells panned from day 8 cells enhanced the response of unprimed cells to native cyt.c. Elimination of B cells demonstrated that primary recognition of cyt.c was mediated, at least partly, by non-specific antigen-presenting cells (APC) while later B cells of additional specificities were involved. It is concluded that immunization with horse cyt.c initiated an autoimmune response resulting in T-dependent anergy. Peptide determinants processed by non-specific APC stimulated corresponding autoreactive T cells. Specific B cells which appeared as a result of the response maturation processed successfully the immunodominant epitope and finally mediated proliferative and antibody responses.
Palladin Institute of Biochemistry, Kiev, Ukraine.
M V
MV
Skok
S V
SV
Komissarenko
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D003574:Cytochrome c Group / Q000276:immunology*; D006736:Horses; D007109:Immunity / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C
D003574:Cytochrome c Group; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G