T Cell Costimulation Mechanisms in Immune Responses
Summary
T cell activation is governed by a dual-signal paradigm in which the antigen-specific engagement of the T-cell receptor (TCR) (Signal 1) must be complemented by costimulatory signals (Signal 2) to achieve full activation, proliferation and differentiation. Principal among costimulatory receptors is CD28, which binds CD80 and CD86 on antigen-presenting cells to amplify downstream pathways such as PI3K–AKT and NF-κB, promoting interleukin-2 production, cell cycle entry and survival. In the absence of appropriate costimulation, T cells become anergic or undergo deletion, ensuring self-tolerance. Conversely, inhibitory receptors such as CTLA-4 and PD-1 compete for the same ligands or recruit phosphatases to attenuate activation, shaping effector versus regulatory programmes. The balance of positive and negative signals at the immune synapse influences lineage commitment, memory formation and the strength of effector responses, with direct relevance to autoimmunity, infection control and immunotherapy.
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T Cell Costimulation Mechanisms in Immune Responses publication trend
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Technical terms
T-cell receptor (TCR): Antigen-recognising complex on T cells that initiates cellular activation upon peptide–MHC engagement.
Costimulatory molecule: Cell-surface protein providing secondary signals essential for full T-cell activation, survival and differentiation.
CD28: Principal costimulatory receptor on T cells that binds CD80/CD86 ligands to enhance proliferation, cytokine production and survival.
CD80/CD86: Ligands on antigen-presenting cells that engage CD28 to deliver costimulatory signals necessary for effective T-cell responses.
Immune synapse: Organised interface between a T cell and an antigen-presenting cell where antigen recognition and costimulatory interactions occur.
Anergy: State of T-cell unresponsiveness induced when antigen recognition occurs without adequate costimulation.
References
- Differential Impact of CD43 and CD28 on T-Cell Differentiation Depending on the Order of Engagement with the TCR. International Journal of Molecular Sciences (2024).
- A B7-H3-targeted CD28 bispecific antibody enhances the activity of anti-PD1 and CD3 T-cell engager immunotherapies. Molecular Cancer Therapeutics (2024).
- Genomic profiling of T-cell activation suggests increased sensitivity of memory T cells to CD28 costimulation. Genes & Immunity (2020).
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