Function of Granule Perform and Esterases in T Cell‐Mediated Reactions: Components Required for Delivery of Molecules to Target Cells

ECKHARD R. PODACK, DAVID M. LOWREY, MATHIAS LICHTENHELD, ARIF HAMEED

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Cognate T cell-mediated functions require antigen and MHC-restricted recognition of target cells. T-effector functions comprise the delivery of signals for help, for suppression, or for cell death of the target cell. In the case of the delivery of cytotoxicity and of help for B-cell antibody production, it is known that the secretory apparatus of the effector cell participates. Prior to secretion, many components of the effector cell are stored in cytoplasmic granules. Among the important and apparently constant constituents of granules are pore-forming proteins (perforins) and proteinases (granzymes). The putative role of perforin has been thought to mediate direct cytotoxicity. It is postulated here that, in addition, perforin at low concentrations may induce target-cell endocytosis through the formation of Ca channels. Localized endocytosis of the target at the contact site in turn may lead to the uptake of locally secreted effector-cell factors, such as cytotoxic factors (CTL), lymphokines (helper cells), or suppressor factors (suppressor cells). The potential importance of such a mechanism is the delivery and uptake of secreted effector-cell components into the endosomes of target cells, bypassing the need for appropriate target-cell receptors. Perforin thus may subserve two functions depending on its intragranular concentration: one, as a killer molecule, and two, as a delivery system for additional granule factors.

Original languageEnglish (US)
Pages (from-to)292-302
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume532
Issue number1
DOIs
StatePublished - Aug 1988

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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