Cytotoxic T-lymphocyte antigen-4 (CTLA-4)

CTLA-4 (CD152) is a member of the immunoglobulin super family and is in the T-cell cytoplasm, and is expressed in CD4 + and CD8+ T cells and regulatory T cells.

The initial stage of activation of the immune response occurs mainly in the lymph nodes, as the first signal comprises T-cell receptor recognition of specific antigens presented by major histocompatibility complexes on antigen presenting cell (APC).

CTLA‐4 is expressed on the surface of CD4‐positive and CD8‐positive lymphocytes and competes with the T‐cell–costimulatory receptor CD28 for binding to T‐cell–costimulatory factors, which are expressed on the surface of antigen‐presenting cells in the early phase of the immune response.


It is a protein receptor that like PD-L1, works to down regulate the immune system’s natural response to attack tumor cells and generally expressed on Tregs.

The second is a costimulatory receptor activation involving the finding of CD28 on T-cell surface with its CD80 and CD86 ligands on the APC, a required steps T-cell activation and expansion.

CTLA-4 is a co-inhibitory T-cell receptor that competes with CD28 for binding with its APC ligands, which can inhibit T-cell activation.

CTLA-4 is expressed on regulatory T-cells involved in suppressing the activity of cytotoxic T-cells.

CTLA-4 inhibits AKT phosphorylation by using protein phosphatase 2A to mediate the suppression of T cell activation.

There is some suggestion that CTLA-4 may deplete T regulatory cells in the tumor microenvironment.

Anti- CTLA antibodies are thought to inhibit the negative regulatory molecule CTLA-4, which functions at the activation stage of T cell priming.

A negative regulator of the immune system with a key role in endogenous and vaccine induced antitumor immunity.

CTLA-4 plays in important role in preventing auto immunity by preventing excessive T cell activation.

After T cell activation, within 48 to 72 hours the CTLA-4 migrates to the surface of the T cell.

With the exception of T regulatory cells CD4+, CD25+, Foxp3+, resting lymphocytes do not express CTLA-4 on their surface.

Expression of CTLA-4 is upgraded after binding of the T cell receptor.

Up regulation of CT LA-4 on the surface of cytotoxic T cells inhibits proliferation of these cells.

CTLA-4 has a higher affinity for B7 than for CD28 and binds to it preferentially: binding of CTLA-4 to B7 results in an inhibitory signal to the T cell and down regulates the immune response.

CTLs bind to B7-1 and B-7-2 (CD80 and CD86) ligand pair which are expressed on the surface of antigen presenting cells (APCs).

Interaction between CTLA-4 and B7-1/B7-2 activates a cell signaling cascade that results in cell cycle arrest of CTLs leading to T cell anergy and interferes with IL-2 secretion and IL-2 receptor expression.

The above process leads to inhibition of T cell priming, immune escape and tumor growth.

The binding of CD28 on CTLs to B7-1 AND B7-2 can stimulate Tcell proliferation and production of IL-2.

Impairment of the expression of CTLA-4 can result in an autoimmune disease.

Polymorphisms and mutations in the CT LA-4 gene have been associated with insulin dependent diabetes, Graves’ disease, Hashimoto’s thyroiditis, systemic lupus erythematosis, and celiac disease.

Has a key role as a negative regulator in immune activity.

A molecule that down regulates pathways of T cell activation.

Ipilimubab, a fully human monoclonal anti-body that blocks CTLA-4

A close homologue of CD28.

CTLA-4 activate inhibitory signals that converts an activated T cell into an inhibited one, to limit self damage.

Principle role is to induce peripheral immune tolerance in antigen specific T cells by induction of apotosis or functional paralysis, anergy.

Cytotoxic T lymphocytes are key to the antitumor specific response in melanomas, and various melanoma specific clones of such cells have been identified.

Ipilimumab is an CTLA-4 antobody that causes blockade of CTLA-4, resulting in prolonged T cell activation, proliferation and antitumor response.

Leave a Reply

Your email address will not be published. Required fields are marked *