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The co-stimulatory activity of Tim-3 requires Akt and MAPK signaling and immune synapse recruitment
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
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Abstract
- Expression of the transmembrane protein Tim-3 is increased on dysregulated T cells undergoing chronic T cell activation, including in chronic infection and solid tumors. We and others previously reported that Tim-3 exerts apparently paradoxical co-stimulatory activity in T cells (and other cells), including enhancement of ribosomal S6 protein phosphorylation (pS6). Here we examined the upstream signaling pathways that control Tim3-mediated increases in pS6 in T cells. We have also defined the localization of Tim-3 relative to the T cell immune synapse and impacts on downstream signaling. Recruitment of Tim-3 to the immune synapse was mediated exclusively by the transmembrane domain, replacement of which impaired Tim-3 co-stimulation of pS6. Strikingly, enforced localization of the Tim-3 cytoplasmic domain to the immune synapse in the context of a chimeric antigen receptor still allowed for robust T cell activation. Our findings are consistent with a model whereby Tim-3 enhances TCR-proximal signaling under acute conditions.One Sentence SummaryHere we define elements of signaling and localization associated with Tim-3 co-stimulatory function in T cells.
- Subjects :
- 0303 health sciences
Chemistry
T cell
Chimeric antigen receptor
Transmembrane protein
3. Good health
Immunological synapse
Cell biology
03 medical and health sciences
Transmembrane domain
0302 clinical medicine
medicine.anatomical_structure
medicine
Protein phosphorylation
Signal transduction
Protein kinase B
030304 developmental biology
030215 immunology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....f277538ccea40090694c63163f9ddd91