Anti-CD8 Anticorps [MEM-31] (APC) (A85480)

Cytotoxic T-lymphocytes (CTL) kill their targets by cytolytic granule secretion at the immunological synapse. The Sec/Munc protein, Munc18-2, and its binding partner Syntaxin 11 (STX11) are both required for granule secretion, with mutations in either leading to the primary immunodeficiency, Familial Haemophagocytic Lymphohistiocytosis (FHL4 and 5). Understanding how Munc18-2 and STX11 function in CTL has been hampered by not knowing the endogenous localization of these proteins. Using a novel FHL5 Munc18-2 mutation that results in loss of protein, cytotoxicity and degranulation together with CTL from an FHL4 patient lacking STX11, enabled us to localize endogenous STX11 and Munc18-2 in CTL. Munc18-2 localized predominantly to cytolytic granules with low levels associated with the plasma membrane where STX11 localized. Importantly, while Munc18-2 localization is unaffected by the absence of STX11 in FHL4 CTL, STX11 is lost from the plasma membrane in FHL5 CTL lacking Munc18-2. These findings support a role for Munc18-2 in chaperoning STX11 to the plasma membrane where the final fusion events involved in secretion occur.

Monoclonal antibodies against several human leucocyte cell surface antigens were prepared and characterized: B2M-02, a non-cytotoxic antibody against beta-2-microglobulin; MEM-09 and MEM-40, against immunoglobulin kappa-type light chains; MEM-12, MEM-24G and MEM-32B, all against a monomorphic determinant in MHC class II antigens, presumably HLA-DR, dependent on the association of alpha and beta chains; MEM-15 and MEM-18, against a monocyte antigen of 55 kDa; MEM-28, against a 200 kDa antigen expressed on all leucocytes; MEM-31, against the T8 antigen of the cytotoxic/suppressor T-lymphocyte subpopulation; MEM-32, against the T1 antigen of T lymphocytes.