CTLA-4 and T cell activation

doi:10.1016/S0952-7915(99)80047-8

Current Opinion in Immunology

Volume 11, Issue 3, June 1999, Pages 294-300

https://doi.org/10.1016/S0952-7915(99)80047-8 Get rights and content

The past year has seen significant advances in our understanding of the role of cytotoxic T lymphocyte antigen 4 (CTLA-4) in regulating T cell activation and tolerance. Recent studies indicate that CTLA-4 not only counterbalances CD28 signals but also can inhibit T cell responses independently of CD28. Recent work has also revealed a role for CTLA-4 in regulating Th1 /Th2 differentiation. Manipulation of CTLA-4 in animal models of autoimmunity has shown that CTLA-4 regulates both the initiation and the progression of autoimmune diseases.

References and recommended reading (2)

LenshowDJ et al.
CD28/B7 system of T cell costimulation
Annu Rev Immunol
(1996)
McAdamAJ et al.
The role of B7 co-• stimulation in activation and differentiation of CD4⁺ and CD8⁺ T cells
Immunol Rev
(1998)

Cited by (180)

Prediction of CD28-CD86 protein complex structure using different level of resolution approach
2021, Journal of Molecular Graphics and Modelling
Citation Excerpt :
Both proteins are strictly involved in cellular immune T-cell responses [4]. Human CTLA-4 is structurally related to CD28 with approximately 30% sequence identity (27, 30, and 29% identity for V-type, TM and cytoplasmic domains, respectively) [5], however CTLA-4 and CD28 play an opposite role in T-cells activation [6,7]. CTLA-4 suppresses T-cells, therefore calms autoimmune responses [8], while CD28 promotes the T-cell activation upon the ligand binding.
Immune system plays essential role in functioning of higher organisms. Its hyperactivity can lead to autoimmune diseases or even anaphylactic shock while hypoactivity leads to proneness to infections or even cancer. T-cells play crucial role in immunity mechanisms and their activation and inhibition is strictly controlled by the regulatory proteins, such as CD28 and CTLA-4. Activity of these proteins is controlled by a pair of ligands, named CD80 and CD86, which can non-covalently bound to their receptors. While structure of human CTLA-4-CD86 complex in known, there is still no available structure for the CD28-CD86 system. To obtain the reliable structure of CD28-CD86 complex we first validated our methodology on the CTLA-4-CD86 system. Then coarse-grained UNRES-dock molecular docking simulation was performed followed by all-atom molecular dynamics simulations. As a result, we obtained a complete CD28-CD86 complex structure on atomistic level, in which interaction interface is consistent with available data. We also determined the kinetic properties for CTLA4-CD86 and CD28-CD86 complexes with use of coarse-grained model and determined the key residues for complex formation with use of Robetta, PPCheck and HawkDock servers. Our results not only verify high accuracy of the UNRES-dock method, but also provide a highly reliable model of the CD28-CD86 complex, which can be used in further studies and drug design.
CTLA-4 and IL-6 gene polymorphisms: Risk factors for recurrent pregnancy loss
2016, Human Immunology
The purpose of the present study was to evaluate the possible association between CTLA-4 +49A/G and IL-6 −634C/G polymorphisms, and the risk of recurrent pregnancy loss (RPL). 240 women (120 healthy controls and 120 with RPL) were enrolled in this case-control study. Genotyping was performed using a PCR-RFLP technique. In the case of polymorphic CTLA-4 +49A/G, the wild type allele G was associated with a decreased risk of RPL (OR: 0.42, 95%CI: 0.25–0.69, p = 0.001). As to IL-6 −634C/G polymorphism, a highly significant difference was observed, and those women who carry at least one mutant G allele presented a probability of developing RPL about 5 times greater than controls (OR: 5.1, 95%CI: 1.04–25.3, p = 0.04). The results indicate that polymorphisms of CTLA-4 and IL-6 genes may influence the risk of developing RPL among Iranian women, suggesting that more research on the immunogenetics of pregnancy should be conducted to confirm our results, and to declare the exact roles of studied molecules in RPL pathogenesis.
Anti-PD-L1-Based Bispecific Antibodies Targeting Co-Inhibitory and Co-Stimulatory Molecules for Cancer Immunotherapy
2024, Molecules
Correlation of CTLA-4 polymorphism and the risk of gastric cancer in a Chinese Bai population
2023, International Journal of Immunogenetics
Beyond the Clinic: The Activation of Diverse Cellular and Humoral Factors Shapes the Immunological Status of Patients with Active Tuberculosis
2023, International Journal of Molecular Sciences
Current understanding of CTLA-4: from mechanism to autoimmune diseases
2023, Frontiers in Immunology

View all citing articles on Scopus

View full text

CTLA-4 and T cell activation

CD28/B7 system of T cell costimulation

Annu Rev Immunol

The role of B7 co-• stimulation in activation and differentiation of CD4+ and CD8+ T cells

Immunol Rev

The role of B7 co-• stimulation in activation and differentiation of CD4⁺ and CD8⁺ T cells