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International Immunology, Vol. 11, No. 11, 1731-1738, November 1999
© 1999 Japanese Society for Immunology

Antigen-induced TCR–CD3 down-modulation does not require CD3{delta} or CD3{gamma} cytoplasmic domains, necessary in response to anti-CD3 antibody

Valérie Legendre, Annick Guimezanes, Michel Buferne, Marc Barad, Anne-Marie Schmitt-Verhulst and Claude Boyer

Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseilles, Cedex 9, France

Correspondence to: C. Boyer

We studied cytotoxic T lymphocyte (CTL) clones expressing cytoplasmic domain-deleted CD3{delta} and CD3{gamma} chains. These cells retained efficient antigen-specific cytolysis. Because the cytoplasmic domains of native CD3{delta} and CD3{gamma} chains contain a dileucine-based and a tyrosine-based motif thought to be important for receptor endocytosis, we compared TCR–CD3 down-modulation on the CTL clones expressing or not these domains. We found that antigen-induced TCR–CD3 down-modulation was not dependent on either the CD3{delta} or CD3{gamma} cytoplasmic domains. This contrasts with phorbol ester- and anti-CD3 mAb (soluble or plastic-coated)-induced TCR–CD3 down-modulation, that are respectively dependent on CD3{gamma} and on either CD3{delta} or CD3{gamma} cytoplasmic domains, suggesting that differences may exist between the mechanisms of TCR–CD3 down-modulation in response to the three stimuli. TCR–CD3 down-modulation in response to antigen was demonstrated by confocal microscopy to be associated with TCRß chain internalization, whether CD3{delta} and CD3{gamma} were native or truncated. Inhibition by the protein tyrosine kinase inhibitor PP1 of TCR–CD3 down-modulation in response to antigen was also similar whether CD3{delta} and CD3{gamma} cytoplasmic domains were present or not. These properties of receptor down-modulation are discussed with respect to the requirements for TCR engagement on antigen-presenting cells.

Keywords: cell–cell interactions, cytotoxic T lymphocyte, protein kinases, rodent, TCR

Transmitting editor: M. M. Davis


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