Antigen-receptor interaction requirement for conjugate formation and lethal-hit triggering by cytotoxic T lymphocytes can be bypassed by protein kinase C activators and Ca2+ ionophores.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 84 ·No. 5 ·1987-03-00 ·Pages 1364-8

Berrebi G, Takayama H, Sitkovsky MV

Abstract

We show that phorbol esters and Ca2+ ionophores can trigger the lysis of nonantigen-bearing target cells by cytotoxic T lymphocytes. This effect obviates the requirement for antigen-receptor-mediated recognition of the antigen; the intensity of lysis is dose and Ca2+ dependent and requires contact between cytotoxic T lymphocytes and target cells. Using a fluorescence-activated cell sorter to enumerate cytotoxic T lymphocyte-target cell conjugates, we show that phorbol esters at concentrations that triggered lysis of non-antigen-bearing target cells also increased the number of stable conjugates with these target cells. The results point to the importance of the antigen-nonspecific engagements of cytotoxic T lymphocytes in immunologic surveillance. The data also show that the linkage between the T-cell receptor and antigen is not mandatory for conjugate formation, for the strengthening of conjugates, and for lysis.

MeSH Terms

Animals Calcimycin/pharmacology Calcium/metabolism Cell Line Cytotoxicity, Immunologic/drug effects Edetic Acid/pharmacology Egtazic Acid/pharmacology Enzyme Activation Ethers/pharmacology Ionomycin Kinetics Mice Mice, Inbred BALB C Protein Kinase C/metabolism Receptors, Antigen, T-Cell/drug effects,immunology T-Lymphocytes, Cytotoxic/drug effects,immunology Tetradecanoylphorbol Acetate/pharmacology

Chemicals

Ethers Receptors, Antigen, T-Cell Calcimycin Egtazic Acid Ionomycin Edetic Acid Protein Kinase C Tetradecanoylphorbol Acetate Calcium

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Berrebi G

Takayama H

Sitkovsky M V

References (34)

34 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.84.5.1364

Published

1987-03-00

Pages

1364-8

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC304430

Subset

External Links

PubMed source DOI: 10.1073/pnas.84.5.1364 PMC Full Text View journal details

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Antigen-receptor interaction requirement for conjugate formation and lethal-hit triggering by cytotoxic T lymphocytes can be bypassed by protein kinase C activators and Ca2+ ionophores.

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