A SECRETED PEPTIDASE INVOLVED IN T-CELL BETA-ENDORPHIN METABOLISM

beta-endorphin metabolism by CD4(+) and CD8(+) T cells, and the thymom a cell line, EL4, was investigated. In all three cell types, extracell ular beta-endorphin was metabolized exclusively by a secreted, metal-d ependent, thiol peptidase. The enzyme activity is expressed constituti vely in EL4 cells and following activation of CD4(+) and CD8(+) T cell s with anti-CD3 antibody. The enzyme is not one of the proteinases ass ociated with cytolytic T cells and does not appear to be identical wit h any previously described beta-endorphin metabolizing enzyme. The enz yme cleaves P-endorphin at approximately equal rates at either of two sites to yield beta-endorphin(1-17) (which is gamma-endorphin), beta-e ndorphin(1-18), beta-endorphin(18-31) and beta-endorphin(19-31). Evide nce in the literature indicates that these N- and C-terminal peptides which contain, respectively, the opioid and non-opioid receptor bindin g domains of beta-endorphin, are biologically active. Thus, it is like ly that this new T cell peptidase has important immunoregulatory activ ity.