A secreted peptidase involved in T cell beta-endorphin metabolism

Beta-endorphin metabolism by CD4+ and CD8+ T cells, and the thymoma cell line, EL4, was investigated. In all three cell types, extracellular beta-endorphin was metabolized exclusively by a secreted, metal-dependent, thiol peptidase. The enzyme activity is expressed constitutively in EL4 cells and following activation of CD4+ and CD8+ T cells with anti-CD3 antibody. The enzyme is not one of the proteinases associated with cytolytic T cells and does not appear to be identical with any previously described beta-endorphin metabolizing enzyme. The enzyme cleaves beta-endorphin at approximately equal rates at either of two sites to yield beta-endorphin(1-17) (which is gamma-endorphin), beta-endorphin(1-18), beta-endorphin(18-31) and beta-endorphin(19-31). Evidence in the literature indicates that these N- and C-terminal peptides which contain, respectively, the opioid and non-opioid receptor binding domains of beta-endorphin, are biologically active. Thus, it is likely that this new T cell peptidase has important immunoregulatory activity.