Target intelligence / Profile preview

T-cell receptor-peptide-Major Histocompatibility Complex (TCR-pMHC complex) (TCR-pMHC)

Target
TCR-pMHC
Molecular classification
Receptor, Protein complex
01

Overview

The T-cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes is the fundamental event in the adaptive immune response, allowing T cells to detect specific antigens (Murphy et al., Janeway's Immunobiology, 2016). This interaction occurs when the TCR on a T cell binds to a peptide fragment presented by a Major Histocompatibility Complex (MHC) molecule on an antigen-presenting cell (APC). Type 1 conventional Dendritic Cells (cDC1) are specialized APCs that are highly efficient at cross-presenting exogenous antigens to CD8+ T cells, making them critical for anti-tumor immunity (Böttcher & Reis e Sousa, 2018, Science). Multi-antigen peptide loading of DC1 cells is a therapeutic strategy used in cancer vaccines to stimulate a broad T-cell response against multiple tumor-associated antigens simultaneously, thereby reducing the risk of immune escape (Sánchez-Paulete et al., 2017, Cancer Discovery). This recognition process is the target of various immunotherapies, including TCR-engineered T cells (TCR-T) and dendritic cell vaccines, which aim to enhance the immune system's ability to identify and destroy malignant or infected cells (June et al., 2018, Science). Modulating this interaction is also key to treating autoimmune diseases, where the goal is to inhibit the recognition of self-antigens.

Other names
TCR-pMHC complexAntigen-MHC complexT-cell receptor-antigen complexcDC1-mediated T-cell activation
02

Mechanism of action

The mechanism involves the specific binding of the T-cell receptor (TCR) to a peptide antigen presented by the Major Histocompatibility Complex (MHC) on the surface of an antigen-presenting cell, such as a DC1 cell, which initiates T-cell signaling and activation (Murphy et al., Janeway's Immunobiology, 2016).

03

Biological functions

Immune responseAntigen presentationT-cell activationSignal transductionCell-mediated immunity
04

Disease associations

CancerInfectionAutoimmune disease
05

Safety considerations

Cytokine release syndromeImmune-related adverse events (irAEs)On-target, off-tumor toxicityAutoimmunity
06

Interacting drugs

Sipuleucel-T

4 more in the full profile.

07

Biomarkers

HLA typing (e.g., HLA-A*02:01)TCR V-beta repertoireCD8+ T-cell infiltrationIFN-gamma productionPD-L1 expression

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