Phosphatidylserine binding directly regulates TIM-3 function
| Autor: | Mark A. Lemmon, Nithya Krishnamurthy, Alice Li, Courtney M. Smith |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Immunology & Inflammation
phosphatidylserine T cell TIM-3 T-Lymphocytes Receptors Antigen T-Cell receptors Apoptosis Phosphatidylserines Lymphocyte Activation Ligands Transfection Biochemistry Jurkat cells Antibodies chemistry.chemical_compound Jurkat Cells Phagocytosis CD28 Antigens medicine Humans signalling Phosphorylation Receptor Molecular Biology Phosphatidylserine binding Hepatitis A Virus Cellular Receptor 2 Research Articles Binding Sites Molecular Interactions phosphorylation/dephosphorylation T-cells Macrophages T-cell receptor NF-kappa B CD28 Membrane Proteins Cell Biology Phosphatidylserine Signaling Cell biology medicine.anatomical_structure HEK293 Cells chemistry Interleukin-2 Signal Transduction |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 |
| Popis: | Co-signaling receptors for the T cell receptor (TCR) are important therapeutic targets, with blockade of co-inhibitory receptors such as PD-1 now central in immuno-oncology. Advancing additional therapeutic immune modulation approaches requires understanding ligand regulation of other co-signaling receptors. One poorly understood potential therapeutic target is TIM-3 (T cell immunoglobulin and mucin domain containing-3). Which of TIM-3's several proposed regulatory ligands is/are relevant for signaling is unclear, and different studies have reported TIM-3 as a co-inhibitory or co-stimulatory receptor in T cells. Here, we show that TIM-3 promotes NF-κB signaling and IL-2 secretion following TCR stimulation in Jurkat cells, and that this activity is regulated by binding to phosphatidylserine (PS). TIM-3 signaling is stimulated by PS exposed constitutively in cultured Jurkat cells, and can be blocked by mutating the PS-binding site or by occluding this site with an antibody. We also find that TIM-3 signaling alters CD28 phosphorylation. Our findings clarify the importance of PS as a functional TIM-3 ligand, and may inform the future exploitation of TIM-3 as a therapeutic target. |
| Databáze: | OpenAIRE |
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