Journal article

Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL

Misty R Jenkins, Jane C Stinchcombe, Byron B Au-Yeung, Yukako Asano, Alex T Ritter, Arthur Weiss, Gillian M Griffiths

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2014

Abstract

T cell receptor (TCR) activation leads to a dramatic reorganisation of both membranes and receptors as the immunological synapse forms. Using a genetic model to rapidly inhibit Zap70 catalytic activity we examined synapse formation between cytotoxic T lymphocytes and their targets. In the absence of Zap70 catalytic activity Vav-1 activation occurs and synapse formation is arrested at a stage with actin and integrin rich interdigitations forming the interface between the two cells. The membranes at the synapse are unable to flatten to provide extended contact, and Lck does not cluster to form the central supramolecular activation cluster (cSMAC). Centrosome polarisation is initiated but abort..

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University of Melbourne Researchers

Grants

Awarded by Wellcome Trust


Awarded by Australian National Health and Medical Research Council (NHMRC) Biomedical Fellowship


Awarded by Arthritis Foundation


Awarded by NIAMS, National Institutes of Health


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

Wellcome Trust 075880, 100140 Gillian M GriffithsHoward Hughes Medical Institute Arthur WeissAustralian National Health and Medical Research Council (NHMRC) Biomedical Fellowship 567082 Misty R JenkinsArthritis Foundation 5476 Byron B Au-YeungNIAMS, National Institutes of Health RC2AR058947 Arthur Weiss