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Major histocompatibility complex molecule and T-cell receptor (as two distinct but functionally paired immune molecules) (MHC (major histocompatibility complex), TCR (T-cell receptor))

Target
MHC (major histocompatibility complex), TCR (T-cell receptor)
Molecular classification
Major histocompatibility complex molecule: Other (antigen-presenting glycoprotein), T-cell receptor: Receptor (immune cell receptor), Immunoglobulin superfamily member
01

Overview

The **major histocompatibility complex (MHC) molecule** is a highly polymorphic glycoprotein that presents peptide antigens on the cell surface, enabling the immune system—specifically T cells—to recognize infected or aberrant cells. The **T-cell receptor (TCR)** is an antigen-specific receptor on the surface of T lymphocytes that recognizes these peptide-MHC complexes and, upon binding, initiates signaling that can activate, regulate, or kill target cells[1][2][3][4]. MHC and TCR work cooperatively: MHC molecules present peptides, while the TCR scans these complexes for foreign or abnormal epitopes, a partnership critical for adaptive immunity, self-tolerance, and protection against infectious and malignant diseases. Polymorphism of MHC genes restricts T cell responses to specific peptide/MHC combinations (“MHC restriction”), contributing to immune diversity, disease susceptibility, and challenges in transplantation[3][4].

Other names
MHCHuman leukocyte antigen (HLA, in humans)TCRCD3–TCR complex
02

Mechanism of action

Drugs may inhibit TCR signaling pathways to reduce T cell activation in transplantation or autoimmunity (e.g., calcineurin inhibitors suppress TCR-mediated transcriptional signals) Immunotherapies in oncology may exploit MHC/TCR interactions (e.g., checkpoint inhibitors, engineered TCR therapies)

03

Biological functions

Immune response (antigen recognition and activation of T cells)Signal transduction (TCR-mediated signaling upon antigen recognition)Self/non-self discrimination (permitting tolerance of self-peptides and response to foreign antigens)Positive and negative selection in T cell maturation (thymic selection)
04

Disease associations

Infection (immune response to pathogens)Cancer (tumor immune surveillance and evasion)Autoimmune disease (dysregulated recognition of self-antigens; specific MHC alleles confer risk, e.g. HLA-B27 in spondyloarthropathies)Organ transplantation (allorecognition, transplant rejection)
05

Safety considerations

Autoimmunity risk if tolerance mechanisms fail or if T cell activation is excessiveImmunodeficiency or infection risk with immunosuppressive therapies targeting TCR signalingGraft rejection in transplantation (MHC incompatibility)
06

Interacting drugs

Immunosuppressants affecting TCR signaling: Cyclosporine

3 more in the full profile.

07

Biomarkers

MHC alleles as disease risk markers (e.g., HLA-B27 for ankylosing spondylitis)T cell receptor clonality and repertoire for immune monitoring in cancer and infection

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