| Description : |
CD28 is the founding member of a subfamily of structurally homologous costimulatory or immune checkpoint molecules of the immunoglobulin (Ig) superfamily. The CD28/B7 pathway has been shown to play a central role in immune responses against infection, autoimmune diseases, and graft rejection (1). CD28 subfamily members, including ICOS, CTLA4, PD1, PD1H, and BTLA, are characterized by a single Ig V-like extracellular domain (ECD), a transmembrane domain and an intracellular domain with highly conserved tyrosine-based signaling motifs (2). CD28 and ICOS predominately enhance T-cell activation, while CTLA-4, PD-1 and BTLA are inhibitory (1-3). The mature ECD of human CD28 shares 65% and 66% amino acid sequence identity with mouse and rat CD28, respectively. CD28 and CTLA-4, together with their ligands, B7-1 and B7-2, constitute one of the dominant co-stimulatory pathways that regulate T and B cell responses. CD28 is expressed on approximately 80% of CD4+ T cells and 50% of CD8+ T cells in humans, with the proportion of CD28-positive T cells declining with age (1-4). CD28 expression has been identified on other cell lineages, including bone marrow stromal cells, plasma cells, neutrophils, and eosinophils (5). CD28 is expressed on the cell surface as a disulfide-linked homodimer and the covalent bond is required for maximum activity (6,7). Although both CTLA-4 and CD28 can bind to the same ligands, CTLA-4 binds to B7-1 and B7-2 with a 20-100 fold higher affinity than CD28. While, CD28 ligation is critical in promoting proliferation and effector function of conventional T cells, it also promotes the anti-inflammatory function of Treg cells. Thus, CD28 serves both pro- and anti-inflammatory roles depending on the cell type and context in which it is expressed (8). The CD28 pathway has effects both at amplifying signals initiated by the T cell receptor and on a variety of processes, including signaling, metabolism, transcription, epigenetic modifications, post-translational modifications, and RNA splicing (9).Our Avi-tag Biotinylated CD28 features biotinylation at a single site contained within the Avi-tag, a unique 15 amino acid peptide. Protein orientation will be uniform when bound to streptavidin-coated surface due to the precise control of biotinylation and the rest of the protein is unchanged so there is no interference in the protein's bioactivity. |
