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 tri gger a specific immune response characterized mainly by CD4(+) T lymph ocytes. They are recognized by T cells under a processed form and in a MHC class II-restricted fashion. IgG degradation which occurs in anti gen-presenting cells (APC) has been studied in vitro. We have shown th at partial reduction of this antigen is an early event which is signif icant for the generation of class Ii-restricted fragments presentable to antigen-specific T cells. Two different murine mAb were used as ant igens and human monocytic U937 or antigen non-specific Epstein-Barr vi rus-transformed a cells as APC. Upon cellular internalization IgG are rapidly cleaved leading to 24-25 kDa fragments. One of the major and e arly events corresponds to partial reduction of IgG-the light chain is released from the intact molecule, heavy chains remaining bound toget her. Partial in vitro reduction of IgG followed by presentation by fix ed a cells to specific T cells showed that only kappa light chain-spec ific T cell clones are stimulated, in contrast to heavy chain-specific T cell clones. The response to the kappa chains of specific T cells p oints to a significant role played by the early IgG partial reduction in the generation of kappa light chain class II binding fragments.