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Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells

Wong, C, Darby, JM, Murphy, PR, Pinfold, TL ORCID: 0000-0002-0506-6389, Lennard, PR, Woods, GM ORCID: 0000-0001-8421-7917, Lyons, AB ORCID: 0000-0002-8508-5853 and Flies, AS ORCID: 0000-0002-4550-1859 2021 , 'Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells' , Developmental and Comparative Immunology, vol. 115 , pp. 1-7 , doi: 10.1016/j.dci.2020.103882.

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Abstract

Immune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumors. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.

Item Type: Article
Authors/Creators:Wong, C and Darby, JM and Murphy, PR and Pinfold, TL and Lennard, PR and Woods, GM and Lyons, AB and Flies, AS
Keywords: immune checkpoint, wild immunology, transmissible cancer, trans-endocytosis, trogocytosis, intercellular protein transfer
Journal or Publication Title: Developmental and Comparative Immunology
Publisher: Pergamon-Elsevier Science Ltd
ISSN: 0145-305X
DOI / ID Number: 10.1016/j.dci.2020.103882
Copyright Information:

Copyright 2020 Elsevier Ltd

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