A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells.
We define a novel Bcl-x isoform, Bcl-x gamma, that is generated by alternative splicing and characterized by a unique 47 amino acid C-terminus. Bcl-x gamma is expressed primarily in thymocytes, where it may depend on an interaction between the TCR and host MHC products, and in mature T cells, where its expression is associated with ligation of the T cell receptor. Overexpression of Bcl-x gamma in T cells inhibits activation-induced apoptosis; inhibition of Bcl-x gamma, after stable expression of Bcl-x gamma antisense cDNA, enhances activation-induced apoptosis. In contrast to other Bcl-x isoforms, cells that fail to express Bcl-x gamma after CD3 ligation undergo programmed cell death, while activated T cells that express Bcl-x gamma are spared. Identification of Bcl-x gamma helps provide a molecular explanation of T cell activation and death after antigen engagement.
Yang
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Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Weber
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Cantor
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D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008969:Molecular Sequence Data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D014018:Tissue Distribution; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D051020:bcl-X Protein