Receptor-mediated B cell antigen processing. Increased antigenicity of a globular protein covalently coupled to antibodies specific for B cell surface structures.
Helper T cell recognition of globular protein antigens requires the intracellular processing of the native molecule by an antigen-presenting cell and subsequent presentation of a peptide fragment, containing the antigenic determinant, on the cell surface where it is recognized by the specific T cell in conjunction with Ia. B lymphocytes can function as antigen-presenting cells and, when antigen is bound by their surface Ig, are greatly enhanced in this capacity. In this report it is demonstrated that pigeon cytochrome c covalently coupled to antibodies directed toward either B cell surface immunoglobulin, class I or class II are effectively processed and presented by B cells to cytochrome c-specific T cells, requiring up to 1000-fold less cytochrome c as compared with cytochrome c alone or cytochrome c coupled to nonspecific immunoglobulin. The potent activity of the cytochrome c-antibody conjugates appears to be due to the ability of B cells to concentrate the antigen when the process becomes receptor mediated rather than to a signal provided to the B cell by the conjugate binding, because cytochrome c was not more effectively presented in the presence of unconjugated antibodies as compared with cytochrome c alone. Furthermore, the binding of the native antigen to B cell surfaces is not alone sufficient for T cell activation, in that the cytochrome c-antibody conjugates require processing and are major histocompatibility complex restricted. The results presented here indicate that surface immunoglobulin is not unique in its ability to facilitate antigen processing and/or presentation and that Ig, class I and class II are capable of transporting the cytochrome c to a cytoplasmic vesicle where proteolysis occurs yielding the required peptide, minimally of 10 amino acids. Cytochrome c coupled to monovalent fragments of anti-Ig-antibodies was nearly as effectively presented as cytochrome c coupled to bivalent antibodies, indicating that phenomena mediated by bivalent binding, such as patching and capping of the surface Ig, were not required for effective antigen presentation. The cytochrome c-antibody conjugates, which allow antigen processing to be initiated by receptor-mediated endocytosis, may provide the necessary tools to unravel the intracellular processes by which protein antigens are processed and presented by B lymphocytes.
D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D003574:Cytochrome c Group / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000276:immunology
D003574:Cytochrome c Group; D000939:Epitopes; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011947:Receptors, Antigen, B-Cell; D013438:Sulfhydryl Compounds