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Support:

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For Research Use Only. Not for Use in Diagnostic Procedures.

Product Includes Product # Quantity Mol. Wt Isotype/Source
CD3ε (D7A6E™) XP® Rabbit mAb8506120 µl23 kDaRabbit IgG
CD8α (D8A8Y) Rabbit mAb8533620 µl29 kDaRabbit IgG
Tox/Tox2 (E6I3Q) Rabbit mAb7375820 µl60-80 kDaRabbit IgG
TCF1/TCF7 (C63D9) Rabbit mAb220320 µl48, 50 kDaRabbit IgG
Granzyme B (D6E9W) Rabbit mAb4689020 µl30 kDaRabbit IgG
PD-1 (Intracellular Domain) (D4W2J) XP® Rabbit mAb8616320 µl52-65 kDaRabbit IgG
TIGIT (E5Y1W) XP® Rabbit mAb9956720 µl18, 30-40 kDaRabbit IgG
TIM-3 (D5D5R™) XP® Rabbit mAb4520820 µl45-70 kDaRabbit IgG
LAG3 (D2G4O) XP® Rabbit mAb1537220 µl60-80 kDaRabbit IgG
Anti-rabbit IgG, HRP-linked Antibody7074100 µlGoat

Please visit cellsignal.com for individual component applications, species cross-reactivity, dilutions, protocols, and additional product information.

Description

The Human Exhausted CD8+ T Cell IHC Antibody Sampler Kit provides an economical means of characterizing the extent of exhaustion in T cells in formalin-fixed, paraffin-embedded tissue samples.

Storage

Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02% sodium azide. Store at –20°C. Do not aliquot the antibodies.

Background

Cluster of Differentiation 3 (CD3) is a multiunit protein complex expressed on the surface of T cells that directly associates with the T cell receptor (TCR). CD3 is composed of four polypeptides: ζ, γ, ε, and δ. Engagement of the TCR complex with antigens presented in major histocompatibility complexes induces tyrosine phosphorylation in the immunoreceptor tyrosine-based activation motif (ITAM) of CD3 proteins. CD3 phosphorylation is required for downstream signaling through ZAP-70 and p85 subunit of PI-3 kinase, leading to T cell activation, proliferation, and effector functions (1). CD8 is a transmembrane glycoprotein expressed primarily on cytotoxic T cells, but has also been described on a subset of dendritic cells in mice (2,3). On T cells, CD8 is a co-receptor for the TCR, and these two distinct structures are required to recognize antigen bound to MHC Class I. CD8 ensures specificity of the TCR–antigen interaction, prolongs the contact between the T cell and the antigen presenting cell, and recruits the tyrosine kinase Lck, which is essential for T cell activation (2).


Tox, Tox2, and TCF1/TCF7 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. The dynamic expression of these transcription factors help characterize the extent to which a T cell is exhausted and will respond to antigen stimulation (4-8). Granzyme B is a serine protease expressed by cytotoxic T lymphocytes and natural killer (NK) cells and is a key component of immune responses to pathogens and transformed cells (9).

PD-1 (PDCD1, CD279), TIGIT (VSIG9, VSTM3), TIM-3 (HAVCR2), and LAG3 (CD223) 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 (10-15). 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. TIGIT is expressed at low levels on subsets of T cells and 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 natural killer (NK) 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 (10-15).

Trademarks and Patents

Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.

XP is a registered trademark of Cell Signaling Technology, Inc.

U.S. Patent No. 7,429,487, foreign equivalents, and child patents deriving therefrom.

All other trademarks are the property of their respective owners. Visit cellsignal.com/trademarks for more information.

Limited Uses

Except as otherwise expressly agreed in a writing signed by a legally authorized representative of CST, the following terms apply to Products provided by CST, its affiliates or its distributors. Any Customer's terms and conditions that are in addition to, or different from, those contained herein, unless separately accepted in writing by a legally authorized representative of CST, are rejected and are of no force or effect.

Products are labeled with For Research Use Only or a similar labeling statement and have not been approved, cleared, or licensed by the FDA or other regulatory foreign or domestic entity, for any purpose. Customer shall not use any Product for any diagnostic or therapeutic purpose, or otherwise in any manner that conflicts with its labeling statement. Products sold or licensed by CST are provided for Customer as the end-user and solely for research and development uses. Any use of Product for diagnostic, prophylactic or therapeutic purposes, or any purchase of Product for resale (alone or as a component) or other commercial purpose, requires a separate license from CST. Customer shall (a) not sell, license, loan, donate or otherwise transfer or make available any Product to any third party, whether alone or in combination with other materials, or use the Products to manufacture any commercial products, (b) not copy, modify, reverse engineer, decompile, disassemble or otherwise attempt to discover the underlying structure or technology of the Products, or use the Products for the purpose of developing any products or services that would compete with CST products or services, (c) not alter or remove from the Products any trademarks, trade names, logos, patent or copyright notices or markings, (d) use the Products solely in accordance with CST Product Terms of Sale and any applicable documentation, and (e) comply with any license, terms of service or similar agreement with respect to any third party products or services used by Customer in connection with the Products.

Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) [email protected] Web: cellsignal.com
For Research Use Only. Not for Use in Diagnostic Procedures.