Cytolysis by H-2-specific T killer cells. Assembly of tubular complexes on target membranes

Abstract

Cloned T killer cells derived from one-way mixed lymphocyte reactions were characterized with regard to their Lyt phenotype and specificity. Two clones of Lyt-1-2+ phenotype that recognized H-2Dd were selected and examined for their cytolytic function by negative staining and thin section electron microscopy. When incubated with the H-2d target S194, they assemble two types of tubular complexes, polyperforin 1 and 2. Both structures appear to arise by polymerization of precursors that may originate in dense granules and/or Golgi of T killer cells. Polyperforins appear to be associated with vesicles that are released during the lytic reaction and transferred to target membranes as shown by immunoelectron microscopy. Since there is a close correlation between target lysis and the appearance of polyperforins on target membranes, it is suggested that polyperforins take part in the cell-mediated killing reaction. Although polyperforins are different in size and several molecular properties from complement, there are striking similarities between these circular complexes and polyperforin (C9). It is therefore possible that they belong to a closely related family of cytolytic effector molecules.