MOLECULES

Full name: Cytotoxic T-lymphocyte associated protein 4

Aliases: CD152, GSE, GRD4, ALPS5, CD152, IDDM12, and CELIAC3^1,2

Family: Immunoglobulin superfamily¹

Receptors: CTLA-4²

Major cellular sources: CD4+ and CD8+ T cells and Treg cells²

Major cellular targets: T cells^2,3

Disease states associated with: Autoimmune diseases and T-cell–mediated diseases⁵

Major physiologic functions:

• CTLA-4 is constitutively expressed in Treg cells or induced following T-cell activation via CD28 and TCR signaling.^2,3
• CTLA-4 and CD28 receptors share two ligands, CD80 and CD86. CTLA-4 binds costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with a higher affinity and avidity than CD28 on APCs (such as DCs and B cells)with CTLA-4-CD80 forming the highest avidity interaction.^2,3
• CTLA-4 negatively regulates T-cell activation through the inhibition and delay of events associated with T-cell activation. This inhibition counteracts the costimulatory effect of CD28, leading to the concept that CTLA-4 can compete with CD28 for ligand binding and thereby acts as an antagonist of CD28-mediated costimulation, one of the models proposed to explain the mechanism of CTLA-4 function.^2-5
• CTLA-4 functions at the cell surface, but in the absence of the ligand, it is primarily localized in intracellular vesicles.^2,3
• An autoimmune, multisystem, T-cell–mediated disease was found in CTLA-4–knockout mice.⁵

ALPS5: autoimmune lymphoproliferative syndrome, type V; APC: antigen-presenting cell; CD: cluster of differentiation; CELIAC3: celiac disease 3; DC: dendritic cell; GRD4: Ground-like domain-containing protein IDDM12: insulin-dependent diabetes mellitus 12; TCR: T-cell receptor; Treg: regulatory T.