| Product Includes | Product # | Quantity | Mol. Wt | Isotype/Source |
|---|---|---|---|---|
| Tox/Tox2 (E6G5O) Rabbit mAb | 36778 | 20 µl | 60-80 kDa | Rabbit IgG |
| TCF1/TCF7 (C63D9) Rabbit mAb | 2203 | 20 µl | 48, 50 kDa | Rabbit IgG |
| EOMES (D8D1R) Rabbit mAb | 81493 | 20 µl | 75, 85 kDa | Rabbit IgG |
| PD-1 (Intracellular Domain) (D4W2J) XP® Rabbit mAb | 86163 | 20 µl | 52-65 kDa | Rabbit IgG |
| CTLA-4 (E1V6T) Rabbit mAb | 96399 | 20 µl | 25-30 kDa | Rabbit IgG |
| TIGIT (E5Y1W) XP® Rabbit mAb | 99567 | 20 µl | 18, 30-40 kDa | Rabbit IgG |
| LAG3 (D2G4O) XP® Rabbit mAb | 15372 | 20 µl | 60-80 kDa | Rabbit IgG |
| TIM-3 (D5D5R™) XP® Rabbit mAb | 45208 | 20 µl | 45-70 kDa | Rabbit IgG |
| 2B4/SLAMF4/CD244 (D5J9D) Rabbit mAb | 54560 | 20 µl | 70-120 kDa | Rabbit IgG |
| Anti-rabbit IgG, HRP-linked Antibody | 7074 | 100 µl | Goat |
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Description
The Human Exhausted T Cell Antibody Sampler Kit provides an economical means of characterizing the extent of exhaustion in T cells. This kit includes enough antibodies to perform two western blot experiments with each primary antibody.
Storage
Background
Tox, TCF1/TCF7, and EOMES play key roles in T cell development. Tox is also induced by high antigen stimulation during chronic viral infection or cancer, regulating T cell persistence and exhaustion. TCF1/TCF7 preserves the effector function of exhausted T cells during viral infection or cancer. EOMES is a key transcription factor for memory T cells and for full effector differentiation of CD8+ T cells. Expression of EOMES is induced in CD8+ T cells following viral infection and bacterial infection, and high levels of EOMES promotes T cell exhaustion. The dynamic expression of these transcription factors help characterize the extent to which a T cell is exhausted and will respond to antigen stimulation (1-5)
PD-1 (PDCD1, CD279), CTLA-4 (CD152), TIGIT (VSIG9, VSTM3), TIM-3 (HAVCR2), LAG3 (CD223), and 2B4 (SLAMF4, CD244) are immune cell co-inhibitory receptors (also known as immune checkpoints) that negatively regulate T cell function and dampen the immune response to pathogens and cancer. In addition to activated T cells, PD-1 is expressed by activated B cells and monocytes. Following interaction with its ligands, PD-L1 and PD-L2, PD-1 is phosphorylated at ITIM and ITSM motifs leading to recruitment of protein tyrosine phosphatases SHP-1 and SHP-2 and suppression of TCR signaling. CTLA-4 protein is primarily expressed on T cells, including CD8+ cytotoxic T cells, CD4+ helper T cells, and CD4+/FoxP3+ regulatory T cells. CTLA-4 protein competes with CD28 for B7.1 (CD80) and B7.2 (CD86) binding at the cell surface, resulting in downregulation of T cell activity. TIGIT is expressed at low levels on subsets of T cells and natural killer (NK) cells, and is upregulated at the protein level following activation of these cells. TIGIT marks exhausted T cells in the tumor microenvironment and during human immunodeficiency virus (HIV) infection. TIM-3 is expressed by exhausted T cells in the settings of chronic infection and cancer. Tumor-infiltrating macrophages and dendritic cells also express TIM-3. LAG3 is primarily expressed by activated CD4+ T cells, CD8+ T cells, FoxP3+ T regulatory cells (Tregs), and NK cells. 2B4 is a heterophilic cell surface receptor expressed on a variety of immune cells, including NK cells, T cells, eosinophils, mast cells, and dendritic cells. 2B4 has been shown to have both immune stimulatory and inhibitory effects on cells. Co-expression of multiple immune checkpoints help characterize the extent to which a T cell is exhausted and will respond to antigen stimulation. Therapeutic blockade of several of these immune checkpoint receptors is a promising strategy for neoplastic intervention by enabling anti-tumor immune responses (6-13).
- Aliahmad, P. et al. (2012) Curr Opin Immunol 24, 173-7.
- Yao, C. et al. (2019) Nat Immunol 20, 890-901.
- Alfei, F. et al. (2019) Nature 571, 265-269.
- Wang, Y. et al. (2019) Front Immunol 10, 169.
- Li, J. et al. (2018) Front Immunol 9, 2981.
- Schildberg, F.A. et al. (2016) Immunity 44, 955-72.
- Anderson, A.C. et al. (2016) Immunity 44, 989-1004.
- Callahan, M.K. et al. (2016) Immunity 44, 1069-78.
- Ward-Kavanagh, L.K. et al. (2016) Immunity 44, 1005-19.
- Chen, L. and Flies, D.B. (2013) Nat Rev Immunol 13, 227-42.
- Sivori, S. et al. (2002) Proc Natl Acad Sci U S A 99, 4526-31.
- Chauvin, J.M. et al. (2015) J Clin Invest 125, 2046-58.
- Chew, G.M. et al. (2016) PLoS Pathog 12, e1005349.
Background References
Trademarks and Patents
Limited Uses
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