Human Exhausted CD8+ T Cell IHC

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.

a. In the circular model of CD8+ T cell differentiation, naïve T cells (TN) cycle between memory (TM) and exhausted (TE) intermediates before reaching a terminal differentiated state (TT). b. In the linear model, CD8+ T cells differentiate depending on the gradual acquisition of memory- or exhausted-associated genes.

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Voisey  Voisey is a technical support specialist at EnkiLife, proficient in immunology and cell biology. She is committed to providing customers with professional and efficient technical support. Additionally, she  is involved in research on customers' fields of study and designs highly cost-effective solutions for them.