A secreted peptidase involved in T cell β-endorphin metabolism

β-endorphin metabolism by CD4⁺ and CD8⁺ T cells, and the thymoma cell line, EL4, was investigated. In all three cell types, extracellular β-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 β-endorphin metabolizing enzyme. The enzyme cleaves β-endorphin at approximately equal rates at either of two sites to yield β-endorphin_1-17 (which is γ-endorphin), β-endorphin_1-18, β-endorphin_18-31 and β-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 β-endorphin, are biologically active. Thus, it is likely that this new T cell peptidase has important immunoregulatory activity.