Santoro L, Reboul A, Kerblat I, Drouet C, Colomb M G
Centre d'Etudes Nucléaires de Grenoble, INSERM U238, France.
Int Immunol. 1996 Feb;8(2):211-9. doi: 10.1093/intimm/8.2.211.
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.
注射到患者体内的鼠单克隆抗体表现为外源性抗原，并引发主要以CD4 + T淋巴细胞为特征的特异性免疫反应。它们以加工后的形式并以MHC II类限制的方式被T细胞识别。已在体外研究了抗原呈递细胞（APC）中发生的IgG降解。我们已经表明，这种抗原的部分还原是一个早期事件，对于产生可呈现给抗原特异性T细胞的II类限制片段具有重要意义。使用两种不同的鼠单克隆抗体作为抗原，以人单核细胞U937或抗原非特异性爱泼斯坦 - 巴尔病毒转化的B细胞作为APC。细胞内化后，IgG迅速裂解，产生24 - 25 kDa的片段。主要的早期事件之一是IgG的部分还原——轻链从完整分子中释放，重链仍结合在一起。体外对IgG进行部分还原，然后由固定的B细胞将其呈递给特异性T细胞，结果表明，与重链特异性T细胞克隆相比，只有κ轻链特异性T细胞克隆受到刺激。特异性T细胞对κ链的反应表明，早期IgG部分还原在κ轻链II类结合片段的产生中发挥了重要作用。
