CTLA-4

Full name: Cytotoxic T-lymphocyte associated protein 4

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

Family:1 Immunoglobulin superfamily

Receptors:2 CTLA-4

Major cellular sources:2 CD4+ and CD8+ T cells and Treg cells

Major cellular targets:2,3 T cells

Disease states associated with:5 Autoimmune diseases and T-cell–mediated diseases

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.

References:

  • 1.

    NCBI. Gene. CTLA4 cytotoxic T-lymphocyte associated protein 4 [Homo sapiens (human)]. www.ncbi.nlm.nih.gov/gene/1493. Accessed March 11, 2021.

  • 2.

    Rowshanravan B, Halliday N, Sansom DM. Blood. 2018;131:58-67.

  • 3.

    Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Immunity. 1996;4:535-543.

  • 4.

    Krummel MF, Allison JP. J Exp Med. 1996;183:2533-2540.

  • 5.

    Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Immunity. 1995;3:541-547.