Resistance to the pore forming protein of cytotoxic T cells: comparison of target cell membrane rigidity

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Department

Biomedical Sciences

Document Type

Article

Publication Title

Molecular Immunology

ISSN

0161-5890

Volume

27

Issue

9

DOI

10.1016/0161-5890(90)90149-T

First Page

839

Last Page

845

Publication Date

9-1-1990

Abstract

Cytotoxic T lymphocytes (CTL) release from their granules a 70 kDa protein, called PFP, perforin or cytolysin, which inserts into the target cell plasma membrane in its monomeric form. Here it polymerizes into a macromolecular complex forming pores as large as 20 nm. Although purified PFP/perforin can effectively lyze all target cells tested, CTL are refractory to lysis. The mechanism underlying the resistance of CTL is currently unknown. This study represents a search for membrane structural properties that could confer resistance to CTL against PFP/perforin-mediated lysis. The fluorescent dye merocyanine 540 was used to measure the lipid head group packing of CTL and several target cells, and 1-[4-(trimethylamine)phenyl]-6-phenylhexa-1,3,5-triene was used to estimate the fluidity of the membrane hydrocarbon region. The resistance against PFP/perforin-mediated. lysis was determined by the 51Cr release assay. A comparison of the membrane rigidity with cell resistance led to the conclusion that the membrane lipid structure cannot account for the unusually high resistance of CTL. In particular, the resistant CTL line CTLL-2 has a lipid head group packing that is looser than that of Yac-1, and the sensitive target cells Jy-25 and EL-4 have membrane acyl chains that are less fluid than those of the effector CTLL-R8.

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