Plasma Membrane-associated Proteins with the Ability to Partially Inhibit Perforin-mediated Lysis

Cytolytic lymphocytes have previously been reported to be resistant to the lytic effects of perforin. In this work, plasma membrane proteins from a CTL cell line were fractionated by HPLC, and the eluted fractions were collected based on their ability to inhibit perforin-mediated hemolysis. Three proteins with inhibitory activity were thus purified, the serine esterase MCSP-3/granzyme F and the histones H2B and H3. A commercial source of H2B was able to potently inhibit perforin-mediated lysis, and it was confirmed by FACS analysis that H2B is in fact present on the surface of cytolytic cells. However, H2B was also found on the surface of perforin-susceptible tumor cell lines, indicating that the histones may partially inhibit perforin-mediated lysis in vitro, but that they do not represent the factor conferring specific resistance on cytolytic lymphocytes. The origin of the surface histones and the possible role of the surface MCSP-3/granzyme F are discussed.