T-cell differentiation antigen CD28 (CD28)

T-cell differentiation antigen CD28, commonly known as CD28, is a pivotal co-stimulatory receptor constitutively expressed on the surface of T cells and belongs to the immunoglobulin superfamily [1.2.1, 1.2.4]. It plays a fundamental role in the adaptive immune system by providing the necessary second signal for full T-cell activation following the engagement of the T-cell receptor with an antigen-MHC complex [1.1.3, 1.2.2]. Upon binding its ligands, CD80 (B7-1) and CD86 (B7-2), on antigen-presenting cells, CD28 triggers intracellular signaling pathways that promote T-cell proliferation, survival, and the production of critical cytokines such as interleukin-2 [1.2.1, 1.3.3]. In the absence of this co-stimulatory signal, T cells often enter a state of anergy or undergo apoptosis, making CD28 a key regulator of immune tolerance and response [1.2.1, 1.2.4]. Therapeutically, CD28 is targeted by antagonists to treat autoimmune diseases and prevent organ transplant rejection by dampening unwanted T-cell activity [1.1.3, 1.2.2]. Conversely, CD28 agonists and bispecific antibodies are being developed in oncology to potently activate T cells against tumor cells [1.1.3, 1.2.5]. However, the use of CD28-targeting agents carries significant safety risks, most notably the potential for life-threatening cytokine release syndrome, as demonstrated by the historical failure of the superagonist TGN1412 [1.1.1, 1.2.1].

Other names

CD28 moleculeT-cell-specific surface glycoprotein CD28TP44Cluster of differentiation 28

CD28 acts as a co-stimulatory receptor that, upon binding to its ligands CD80 (B7-1) or CD86 (B7-2), provides the essential second signal for T-cell activation, proliferation, and survival [1.1.3, 1.2.1]. Drugs targeting CD28 either block this interaction to suppress immune responses in autoimmunity and transplantation (antagonists) or stimulate the receptor to enhance anti-tumor immunity (agonists and superagonists) [1.1.3, 1.2.2, 1.2.5].