T-lymphocyte antigen CD28 (CD28)

T-lymphocyte antigen CD28 (CD28) is a cell-surface receptor found primarily on T cells that plays a central role in co-stimulatory signaling essential for T cell activation, proliferation, differentiation, and survival[1][3][5][7][8]. CD28 forms a disulfide-linked homodimer with Ig-like domains and binds with its ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APCs)[1][2]. The interaction between CD28 and its ligands is necessary for full activation of naïve T cells; without this signal, T cells become anergic and do not respond appropriately to antigen. CD28 engagement leads to increased transcription of cytokines such as interleukin-2 (IL-2), stimulation of cell cycle regulators, and enhancement of anti-apoptotic protein expression[5]. CD28 signaling also modulates the magnitude and quality of immune responses, making it a crucial target in both immune activation (cancer immunotherapy) and immune suppression (autoimmunity, transplantation). Therapeutic agents targeting CD28 and its pathway (including CTLA-4 fusion proteins and monoclonal antibodies) have been used clinically and experimentally, but carry significant safety challenges, most notably the potential for life-threatening cytokine storms with superagonist antibodies[7]. The molecule is classified within the immunoglobulin superfamily, and its expression profile and function have diagnostic, therapeutic, and prognostic relevance.

Other names

Cluster of Differentiation 28CD28 moleculeT-cell-specific surface glycoprotein CD28

Blockade of CD28-mediated costimulatory signaling, resulting in immunosuppression for autoimmunity or prevention of transplant rejection (e.g., CTLA-4-Ig recombinant proteins) Direct stimulation (agonistic anti-CD28 antibodies used experimentally to drive T cell proliferation) Blockade or antagonism to prevent pathological immune activation