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CTLA-4 Cytotoxic
T-lymphocyte-
associated
Antigen-4

CTLA-4 Cytotoxic
T-lymphocyte-
associated
Antigen-4

Overview

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is a membrane bound glycoprotein expressed by activated effector T cells (Teffs). It is involved in inhibiting T cell production, upsetting cell cycle progression, and repressing some cytokine production. These effects are mediated through several mechanisms including direct inhibitory effects through the cytoplasmic tail which links to specific signaling molecules as well as competition with CD28-positive co-stimulation for binding to their shared B7 ligands (CD80/CD86) on antigen-presenting cells (APC).1

  • Binding of the CD28 receptor to ligands CD80 or CD86 on an APC provides a co-stimulatory signal requisite for T-cell activation and the consequent inflammatory cascade.2 This interaction is followed by T-cell expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4).3
  • In the normal immune response, CTLA-4 competes for CD28 binding to CD80 and CD86. CTLA-4 has a higher binding affinity for CD80 and CD86 and its binding blocks T-cell activation by CD28.3
  • In addition, CTLA-4 binding delivers a negative signal that downregulates T-cell function and inhibits the excessive expansion of activated T cells.3
CTLA-4 binding delivers a negative signal that down-regulates T-cell function

CTLA-4 binding delivers a negative signal that downregulates T-cell function.3

CTLA-4 Pathway

References

  1. Zhao Y, Yang W, Huang Y, Cui R, Li X, Li B: Evolving Roles for Targeting CTLA-4 in Cancer Immunotherapy. Cell Physiol Biochem. 2018;47:721-734.
  2. Suchard SJ, Davis PM, Kansal S, et al. A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety. J Immunol. 2013;191:4599-4610.
  3. Vasaturo A, Di Blasio S, Peeters DGA, et al. Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go.
    Front Immunol. 2013;4:417.