Human Exhausted T Cell Antibody Sampler Kit

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).