T-lymphocyte activation antigen CD28 (CD28) (CD28)

T-lymphocyte activation antigen CD28 (CD28) is a critical costimulatory receptor constitutively expressed on the surface of T cells and is a member of the immunoglobulin superfamily [1]. It plays a fundamental role in the immune response by providing the 'second signal' required for full T cell activation following the engagement of the T cell receptor (TCR) with an antigen-MHC complex [3]. This costimulatory signal is generated when CD28 binds to its ligands, B7.1 (CD80) or B7.2 (CD86), which are expressed on the surface of professional antigen-presenting cells [2]. Activation of the CD28 pathway leads to the recruitment of signaling molecules like PI3K and Grb2, which ultimately promotes T cell proliferation, survival, and the production of pro-inflammatory cytokines such as interleukin-2 (IL-2) [4]. Because of its central role in immune regulation, the CD28/B7 axis is a primary target for treating autoimmune diseases and preventing organ transplant rejection [5]. Therapeutic agents like Abatacept and Belatacept work by intercepting the B7 ligands to prevent CD28-mediated costimulation, thereby inducing a state of T cell anergy or unresponsiveness [5]. Conversely, while CD28 agonism has been explored for cancer immunotherapy, it carries significant risks, as evidenced by the severe cytokine storm induced by the superagonistic antibody TGN1412 in early clinical trials [4]. Modern drug development also includes selective CD28 antagonists like Lulizumab pegol and FR104, which aim to block costimulation without the broad effects of ligand-binding agents [1].

Other names

CD28 moleculeTp44T-cell-specific surface glycoprotein CD28Cluster of Differentiation 28

The CD28 pathway is modulated by either blocking the interaction between the CD28 receptor and its B7 ligands (CD80/CD86) to induce immunosuppression or by directly targeting the CD28 receptor to either inhibit or stimulate T cell activity [1, 3, 5]. CTLA-4-Ig fusion proteins like Abatacept bind to B7-1/B7-2 to prevent CD28 engagement, while monoclonal antibodies like Lulizumab pegol bind directly to CD28 to block costimulation [5].