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Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells.
- Source :
-
Developmental and comparative immunology [Dev Comp Immunol] 2021 Feb; Vol. 115, pp. 103882. Date of Electronic Publication: 2020 Oct 08. - Publication Year :
- 2021
-
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.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Motifs genetics
Animals
CD28 Antigens antagonists & inhibitors
CHO Cells
CTLA-4 Antigen antagonists & inhibitors
CTLA-4 Antigen genetics
Cells, Cultured
Cloning, Molecular
Cricetulus
Endangered Species
Immune Checkpoint Inhibitors pharmacology
Immune Checkpoint Inhibitors therapeutic use
Intravital Microscopy
Marsupialia metabolism
Mutation
Trogocytosis
B7-1 Antigen metabolism
B7-2 Antigen metabolism
CD28 Antigens metabolism
CTLA-4 Antigen metabolism
Marsupialia immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0089
- Volume :
- 115
- Database :
- MEDLINE
- Journal :
- Developmental and comparative immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33039410
- Full Text :
- https://doi.org/10.1016/j.dci.2020.103882