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CD4+ T-cell receptor recognizing HIV-1 envelope glycoprotein gp120-derived peptides presented by MHC class II (gp120-specific CD4+ TCR)

Target
gp120-specific CD4+ TCR
Molecular classification
T-cell receptor complex, Antigen-specific receptor, Immunoglobulin superfamily, Receptor
01

Overview

The CD4+ T-cell receptor (TCR) recognizing HIV-1 envelope glycoprotein gp120-derived peptides presented by MHC class II is a critical component of the adaptive immune response against Human Immunodeficiency Virus type 1 (HIV-1) (Siliciano et al., 1988, Nature). These TCRs are expressed on the surface of CD4+ T-helper cells and specifically bind to fragments of the viral envelope glycoprotein gp120 when they are displayed by Major Histocompatibility Complex (MHC) class II molecules on antigen-presenting cells (Hioe et al., 2000, International Immunology). This interaction is fundamental for orchestrating the immune system's response, including the activation of B-cells for antibody production and the enhancement of CD8+ cytotoxic T-cell activity (Lanzavecchia, 1985, Nature). In the context of HIV infection, these specific CD4+ T-cells are often the primary targets for viral entry and subsequent depletion, leading to the progressive immunodeficiency characteristic of AIDS (Douek et al., 2002, Nature). Therapeutic strategies targeting or utilizing these TCRs include the development of vaccines designed to elicit robust gp120-specific T-cell help, such as the RV144 trial components (Rerks-Ngarm et al., 2009, NEJM), and experimental TCR-engineered T-cell therapies aimed at restoring or enhancing the anti-viral cellular immune response (Varela-Rohena et al., 2008, Nature Medicine). Understanding the structural basis of this TCR-peptide-MHC interaction is vital for overcoming viral escape mechanisms and improving the efficacy of immunotherapeutic interventions.

Other names
HIV-1 gp120-specific T-cell receptorgp120-reactive CD4+ TCREnvelope-specific T-cell receptorgp120/MHC-II specific TCR
02

Mechanism of action

Antigen-specific activation of CD4+ T-cells via TCR-CD3 complex signaling upon recognition of gp120 peptide-MHC II complexes

03

Biological functions

Antigen recognitionT-cell activationCytokine productionImmune responseSignal transduction
04

Disease associations

InfectionAcquired Immunodeficiency Syndrome
05

Safety considerations

T-cell exhaustionViral escape mutationsImmune senescenceCytokine dysregulationMolecular mimicry
06

Interacting drugs

AIDSVAX

3 more in the full profile.

07

Biomarkers

gp120-specific CD4+ T-cell frequencyInterferon-gamma productionCD154 expressionHLA-DR activationMHC II tetramer binding

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