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Expression and function of the transfected CD8 alpha chain in murine T cell hybridomas
O Kanagawa1, H Nakauchi, R P Sekaly
1Department of Pathology and Medicine, Washington University, St Louis, MO 63110.
Abstract:
Expression and function of mouse and human CD8 (mCD8 and hCD8) alpha chain molecules in mouse T cell hybridomas were analyzed. The expression of cytolytic T lymphocyte-derived CD8 molecules was suppressed in hybridomas established by fusing the BW5147 thymoma to a CD8+ cytolytic T lymphocyte clone, while expression of CD4 remained intact in BW x CD4+ helper T cell hybridomas. However, hybridomas established by fusing a cytolytic T cell clone with BW5147 cell lines, transfected with either the mCD8 alpha or hCD8 alpha chain, expressed the T cell-derived mCD8 beta chain as a CD8 heterodimer (mCD8 alpha/mCD8 beta or hCD8 alpha/mCD8 beta). These data suggest that negative regulatory mechanisms for the mCD8 alpha gene in BW thymoma failed to suppress mCD8 beta gene expression, indicating different regulatory mechanisms for the tightly linked mCD8 alpha and mCD8 beta genes. Analysis of the antigen reactivity of the hybridomas revealed that the human CD8 alpha chain failed to increase the mouse T cell receptor - class I MHC interaction, even as a heterodimeric form with mCD8 beta molecules. However, both the human CD8 alpha homodimer and the heterodimeric form with mCD8 beta were found to be capable of suppressing the class II-restricted T cell response.