Structure and function of human perforin

Abstract

Perforin (P1) is a cytolytic protein with similarity to complement component C9. P1 has been described as a unique component of murine cytolytic T-cell and rat natural killer cell granules Previous studies indicated that human granules and P1 differed from murine granules and P1 in that they appeared to be cytolytically less active and lacked the haemolytic activity characteristic of P1. It has been suggested that P1, like C9, is under the control of the homologous restriction factor. Here we determine the primary structure of human P1, re-examine its functional properties, and address the question of homologous restriction.

Assessment of cytotoxic T-lymphocyte phenotype using the specific markers granzyme B and TIA-1 in cervical neoplastic lesions

“…Activated CD8+ CTL and NK cells.hold cytotoxic granules that contain the lytic products perforin (Lichtenheld et al, 1988), granzymes: a group of highly homologous serine proteases (Jenne and Tschopp, 1988) and the Tcell-restricted intracellular antigen (Tian et al, 1991). Perforin, or pore-forming protein, causes cell lysis by generating small pores in the plasma membrane of the target cell (Lichtenheld et al, 1988).…”

Perforin expression in lymphocytes infiltrated to human colorectal cancer

“…Recent success in the cloning of PFP cDNA (Shinkai et al, 1988a;Lichtenheld et al, 1988;Lichtenheld & Podack, 1989;Lowrey et al, 1989) has allowed the examination of mRNA expression of PFP in killer cells. In the T cell lines, PFP gene expression was ascertained in the cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, but not in helper T (Th) cells (Shinkai et al, 1988a;Lichtenheld et al, 1988).The role of tumour infiltrating lymphocytes (TIL) in the defense mechanism of a tumour-bearing host has been thoroughly reported (Werkmeister et al, 1979). It is known that CTL and NK cells directly kill tumour cells (Reinherz et al, 1979;Lanier et al, 1983;Lanier et al, 1986 (v/v) hydrogen peroxidase, freshly prepared ABC complex (Vectastain R ABC Kit, Vector) was applied and followed by incubation for 30 min.…”

“…Recent success in the cloning of PFP cDNA (Shinkai et al, 1988a;Lichtenheld et al, 1988;Lichtenheld & Podack, 1989;Lowrey et al, 1989) has allowed the examination of mRNA expression of PFP in killer cells. In the T cell lines, PFP gene expression was ascertained in the cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, but not in helper T (Th) cells (Shinkai et al, 1988a;Lichtenheld et al, 1988).…”

An inframe perforin gene deletion in familial hemophagocytic lymphohistiocytosis is associated with perforin expression

“…However, a majority of these genetic defects (12 out of 23) are located in the centre region of the protein which is composed of an amino acid stretch of approximately 300 with homology to the C9 complement. This region is thought to be involved in the pore formation and thus named the membrane attack complex (MAC) domain [19]. The deletion mutation described in the present study is also located in the MAC domain but is associated with a high residual level of perforin expression in T cells and NK cells in contrast to the variants reported so far, with either an undetectable or barely detectable level of perforin expression [8,9,[11][12][13].…”