Immune Checkpoints and the T cell
Amanda Flies, Ph.D.
CTLA-4 prevents T cell activation by competitively inhibiting the co-stimulatory signal through CD28, as CD28’s ligands (B7-1 and B7-2) have a higher affinity/avidity for CTLA-4. CTLA-4 also transmits an inhibitory signal intracellularly, which reduces proliferation and cytokine production.
Abstract
Immune checkpoints are stimulatory or inhibitory signals that play a major role in regulation of the immune system’s function. Interactions between surface molecules on immune cells lead to activation, differentiation and effector function, or inhibition of these activities. T cells, an important member of the adaptive branch of the immune system, are greatly affected by interactions between immune checkpoint molecules, including CD28 ↔ B7-1/B7-2 ↔ CTLA-4 interactions, PD-1 ↔ PD-L1/PD-L2, LAG-3 ↔ MHC, and TIM-3 ↔ galectin-9 interactions. Proliferation, clonal expansion, differentiation into T cell subsets, and effector functions all depend on stimulation or inhibition through these surface molecules. Thus, regulation of T cells by way of blocking or stimulating the immune checkpoints can have significant effects on the function of the immune system. Recent advances in immunotherapy targeting immune checkpoint molecules have demonstrated efficacy in modulating immune reactions to self-tissues in both cancer immunity and autoimmunity. Continued research into this growing field of study is critical for advancing immunotherapeutic treatments against human diseases using immune checkpoint molecules.
Immune Checkpoint Reagents Available from Cell Sciences:
CTLA-4 Fusion Proteins
| Catalog No. | Description |
| CRH030 | Recombinant Human CTLA-4/CD152:Fc Chimera |
| CRH031 | Recombinant Human CTLA-4/CD152:Fc Chimera Non-Lytic |
| CRH032 | Recombinant Human CTLA-4/CD152:Mouse Fc Chimera |
| CRM035 | Recombinant Mouse CTLA-4/CD152:Fc Chimera |
| CRM036 | Recombinant Mouse CTLA-4/CD152:Fc Chimera Non-Lytic |
PD-1 – PD-L1/2 Reagents
| Catalog No. | Description |
| CRH046 | Recombinant Human PD-1/CD279:Fc Chimera |
| CRH047 | Recombinant Human PD-1/CD279:Fc Chimera Non-Lytic |
| CRH036 | Recombinant Human B7-H1/PD-L1/CD274:Fc Chimera |
| CRH037 | Recombinant Human B7-H1/PD-L1/CD274:Fc Chimera Non-Lytic |
| CRH033 | Recombinant Human PD-L2/CD273:Fc Chimera |
| CRH034 | Recombinant Human PD-L2/CD273:Fc Chimera Non-Lytic |
| CRH035 | Recombinant Human PD-L2/CD273:Mouse Fc Chimera |
| CRM044 | Recombinant Mouse PD-1/CD279:Fc Chimera |
| CRM038 | Recombinant Mouse B7-H1/PD-L1/CD274:Fc Chimera |
| CRM039 | Recombinant Mouse B7-H1/PD-L1/CD274:Fc Chimera Non-Lytic |
| CRM037 | Recombinant Mouse PD-L2/CD273:Fc Chimera |
LAG-3 Reagents
| Catalog No. | Description |
| CMH003 | Mouse Anti-Human LAG-3 Clone 17B4 Biotin mAb |
| CMH004 | Mouse Anti-Human LAG-3 Clone 17B4 Blocking Azide Free mAb |
| CMH005 | Mouse Anti-Human LAG-3 Clone 17B4 FITC mAb |
| CMH006 | Mouse Anti-Human LAG-3 Clone 17B4 Blocking mAb |
| CMH007 | Mouse Anti-Human LAG-3 Clone 11E3 Blocking mAb |
| CMH008 | Mouse Anti-Human LAG-3 Clone 11E3 Blocking Azide Free mAb |
| CRH048 | Recombinant Human LAG-3:Fc Chimera |
| CRM045 | Recombinant Mouse LAG-3:Fc Chimera |
TIM-3 Reagents
| Catalog No. | Description |
| CRH050 | Recombinant Human Tim-3:Fc Chimera |
| CRH051 | Recombinant Human Tim-3:Mouse Fc Chimera |
Additional Immune Checkpoint Reagents
| Catalog No. | Description |
| CRH022 | Recombinant Human Multimeric TNF-alpha |
| CRH023 | Recombinant Human Multimeric FasL |
| CRH024 | Recombinant Human Multimeric CD40L |
| CRH025 | Recombinant Human Multimeric APRIL |
| CRH026 | Recombinant Human Progranulin FLAG |
| CRH027 | Recombinant Human Progranulin |
| CRH028 | Recombinant Human B7-H4:Fc Chimera |
| CRH029 | Recombinant Human B7-H4:Mouse Fc Chimera |
| CRH038 | Recombinant Human B7-H2/CD275:Fc Chimera |
| CRH039 | Recombinant Human B7-H2/CD275:Fc Chimera Non-Lytic |
| CRH040 | Recombinant Human B7-H2/CD275:Mouse Fc Chimera |
| CRH041 | Recombinant Human B7-H3/CD276:Fc Chimera |
| CRH042 | Recombinant Human B7-H3/CD276:Mouse Fc Chimera |
| CRH043 | Recombinant Human ICOS/CD278:Fc Chimera |
| CRH044 | Recombinant Human ICOS/CD278:Fc Chimera Non-Lytic |
| CRH045 | Recombinant Human ICOS/CD278:Mouse Fc Chimera |
| CRH049 | Recombinant Human Tim-1:Fc Chimera |
| CRH051 | Recombinant Human Tim-3:Mouse Fc Chimera |
| CRH052 | Recombinant Human Tim-4:Fc Chimera |
| CRM030 | Recombinant Mouse Multimeric CD40L |
| CRM031 | Recombinant Mouse Multimeric OX40L |
| CRM032 | Recombinant Mouse Multimeric APRIL |
| CRM033 | Recombinant Mouse Progranulin |
| CRM034 | Recombinant Mouse B7-H4:Fc Chimera |
| CRM040 | Recombinant Mouse B7-H2/CD275:Fc Chimera |
| CRM041 | Recombinant Mouse B7-H2/CD275:Fc Chimera Non-Lytic |
| CRM042 | Recombinant Mouse B7-H3/CD276:Fc Chimera |
| CRM043 | Recombinant Mouse ICOS/CD278:Fc Chimera |
| CRM046 | Recombinant Mouse Tim-4:Human Fc Chimera |
| CRM047 | Recombinant Mouse CD137:Human Fc Chimera |