CD28 receptor (CD28)

The **CD28 receptor** is a critical co-stimulatory molecule expressed on the surface of T cells. It binds primarily to B7 family ligands—CD80 and CD86—on antigen-presenting cells. This interaction provides the essential "second signal" required for full T-cell activation following engagement of the T cell receptor (TCR) with an antigen-MHC complex. Without this co-stimulation via CD28, T cells become anergic or undergo apoptosis. **CTLA4** (Cytotoxic T-Lymphocyte Antigen 4), also known as **CD152**, is a homologous but functionally antagonistic receptor that competes with CD28 for binding to B7 ligands. While both receptors share similar structures and bind the same ligands, CTLA4 has much higher affinity and acts as a negative regulator by outcompeting CD28 at sites of immune activation. Upon upregulation after initial activation signals, CTLA4 dampens further immune responses by sequestering B7 molecules away from CD28 and delivering inhibitory signals into the cell. This balance between **CD28-mediated stimulation** and **CTLA4-mediated inhibition** is fundamental in regulating adaptive immunity—promoting effective defense against pathogens while preventing autoimmunity. Therapeutic agents such as abatacept and belatacept exploit this pathway by mimicking CTLA4's extracellular domain fused to IgG Fc regions; they block B7-CD28 interactions on APCs, thereby suppressing unwanted immune responses in autoimmune diseases or transplantation. The entry "Co-stimulatory molecule CD28 pathway via CTLA‑4 expression" describes not a single molecular entity but rather an immunoregulatory axis involving two distinct proteins—CD28 (a stimulatory receptor) and CTLA‑4 (an inhibitory checkpoint). For structured data purposes these should be treated separately; otherwise there is ambiguity regarding which molecular target is referenced. *Note*: The provided name conflates two related but distinct targets—the canonical forms are "CD28 receptor" for costimulation, and "Cytotoxic T-Lymphocyte Antigen 4" ("CTLA‑4") for coinhibition.[1][2][3]

Other names

Cluster of Differentiation 28T-cell-specific surface glycoprotein CD28CD28 antigenT-cell co-stimulatory receptor

Blockade of B7-CD28 interaction to inhibit T-cell co-stimulation and activation. Enhancement or inhibition of immune checkpoint signaling via CTLA4 expression/modulation.