[email protected] Questions for the Final: Slide presentation Immunity paper (survivin) Immunity paper (Gr. A induced apoptosis). Cell Mediated Cytotoxicity and Apoptosis. Cytotoxic T cells and granule exocytosis Trafficking of granules to the plasma membrane in CTL
Questions for the Final:
Immunity paper (survivin)
Immunity paper (Gr. A induced apoptosis)
Cell Mediated Cytotoxicity and Apoptosis
CTLs kill target by 2 different mechanisms:
Mice with deficiencies or
mutations in CTL death pathways
Cytotoxic Lymphocyte Granule Components
Granzymes: Subfamily of serine proteases found in the secretory granules of hematopoietic cells
Cytotoxic T lymphocyte granules contain:
1) Granzyme A, with “tryptase” specificity cleaving after arg or lys residues. Measured by the sensitive BLT esterase assay.
2) Granzyme B, with an unusual “aspase” specificity cleaving after asp residues. Can process and activate caspases 3,7,8,9&10.
3) Granzymes C-G, expressed at lower levels, with poorly defined “chymase” specificity. Not detectable in CTL in vivo.
Variations on a theme of lysosomal secretion. Summary of the protein machinery identified in lysosomal secretion in spermatid (acrosomal granule, orange) , platelets, fibroblasts, CTL, melanocytes, and mast cells. Secretion of lysosomes (white) is required for secretion in some cell types and can involve movement along microtubules (black) in a plus or minus direction.
Trafficking of cytolytic granules to the
plasma membrane in CTL
Protein secretion can utilize two export pathways
(Disrupted by Brefeldin A)
From: Molecular Biology of the Cell
Regulation of intracellular membrane vesicle fusion
Pfeffer, Nature Cell Biology 1:E17 (1999)