Monoclonal IgG as antigens: reduction is an early intracellular event of their processing by antigen-presenting cells.
Murine mAb injected into patients behave as exogenous antigens and trigger a specific immune response characterized mainly by CD4+ T lymphocytes. They are recognized by T cells under a processed form and in a MHC class II-restricted fashion. IgG degradation which occurs in antigen-presenting cells (APC) has been studied in vitro. We have shown that partial reduction of this antigen is an early event which is significant for the generation of class II-restricted fragments presentable to antigen-specific T cells. Two different murine mAb were used as antigens and human monocytic U937 or antigen non-specific Epstein-Barr virus-transformed B cells as APC. Upon cellular internalization IgG are rapidly cleaved leading to 24-25 kDa fragments. One of the major and early events corresponds to partial reduction of IgG--the light chain is released from the intact molecule, heavy chains remaining bound together. Partial in vitro reduction of IgG followed by presentation by fixed B cells to specific T cells showed that only kappa light chain-specific T cell clones are stimulated, in contrast to heavy chain-specific T cell clones. The response to the kappa chains of specific T cells points to a significant role played by the early IgG partial reduction in the generation of kappa light chain class II binding fragments.
Santoro
L
L
Centre d'Etudes Nucléaires de Grenoble, INSERM U238, France.
Reboul
A
A
Kerblat
I
I
Drouet
C
C
Colomb
M G
MG
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism*; D000918:Antibody Specificity; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse; D010084:Oxidation-Reduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains