Cytokines & Chemokines

Human CD28 is composed of four exons encoding a protein of 220 amino acids that is expressed on the cell surface as a glycosylated, disulfide-linked homodimer of 44 kDa. Members of the CD28 family share a number of common features. These receptors consist of paired V-set immunoglobulin superfamily (IgSF) domains attached to single transmembrane domains and cytoplasmic domains that contain critical signaling motifs. The CD28 and CTLA4 ligands, CD80 and CD86, consist of single V-set and C1-set IgSF domains. The interaction of these costimulatory receptors with ligands is mediated through the MYPPPY motif within the receptor V-set domains. CD28 is expressed constitutively on almost all human CD4 T cells and approximately 50% of CD8 T cells. CD28 costimulation has diverse effects on T cell function, including biochemical events at the immunological synapse, downstream phosphorylation and other post-translational modifications, transcriptional changes, and cytoskeletal remodeling. At the mo

Human CD28 is composed of four exons encoding a protein of 220 amino acids that is expressed on the cell surface as a glycosylated, disulfide-linked homodimer of 44 kDa. Members of the CD28 family share a number of common features. These receptors consist of paired V-set immunoglobulin superfamily (IgSF) domains attached to single transmembrane domains and cytoplasmic domains that contain critical signaling motifs. The CD28 and CTLA4 ligands, CD80 and CD86, consist of single V-set and C1-set IgSF domains. The interaction of these costimulatory receptors with ligands is mediated through the MYPPPY motif within the receptor V-set domains. CD28 is expressed constitutively on almost all human CD4 T cells and approximately 50% of CD8 T cells. CD28 costimulation has diverse effects on T cell function, including biochemical events at the immunological synapse, downstream phosphorylation and other post-translational modifications, transcriptional changes, and cytoskeletal remodeling. At the mo

B7-1 and B7-2 are homologous costimulatory ligands expressed on the surface of antigen presenting cells (APCs), both are type 1 transmembrane proteins with a membrane distal IgV and a membrane proximal IgC domain. They share ~25% sequence homology and interact with the same receptors, CD28 and CTLA-4.Binding of these molecules to the T cell costimulatory receptors, CD28 and CTLA-4, is essential for the activation and regulation of T cell immunity. T cell activation requires engagement of the T cell receptor (TCR) with the peptide–MHC complex presented on the cell surface of antigen presenting cells (APCs). In addition to this antigen-specific interaction, a second interaction involving costimulatory receptors (CD28, ICOS) on T cells and their respective ligands (B7-1/B7-2, ICOS-L) on APCs is required for optimal T cell activation. B7-1 and B7-2 may also function to deliver signal into dendritic cells. While B7-1 favors binding to CTLA-4, B7-2 shows a preference for CD28.

B7-1 and B7-2 are homologous costimulatory ligands expressed on the surface of antigen presenting cells (APCs), both are type 1 transmembrane proteins with a membrane distal IgV and a membrane proximal IgC domain. They share ~25% sequence homology and interact with the same receptors, CD28 and CTLA-4.Binding of these molecules to the T cell costimulatory receptors, CD28 and CTLA-4, is essential for the activation and regulation of T cell immunity. T cell activation requires engagement of the T cell receptor (TCR) with the peptide–MHC complex presented on the cell surface of antigen presenting cells (APCs). In addition to this antigen-specific interaction, a second interaction involving costimulatory receptors (CD28, ICOS) on T cells and their respective ligands (B7-1/B7-2, ICOS-L) on APCs is required for optimal T cell activation. B7-1 and B7-2 may also function to deliver signal into dendritic cells. While B7-1 favors binding to CTLA-4, B7-2 shows a preference for CD28.

PD-L1 and PD-L2 are ligands for PD-1, a costimulatory molecule that plays an inhibitory role in regulating T cell activation in the periphery. PD-L2 also known as PD-L2, B7-DC serves as a negative and a positive regulator of T cell function. The expression and function of PD-L2 are similar to PD-L1. Both PD-L2−PD-1 and PD-L1−PD-1 signals inhibit T cell proliferation by blocking cell cycle progression but not by increasing cell death. PD-L2−PD-1 interactions are able to inhibit TCR-mediated proliferation and cytokine production in the absence of CD28 costimulation. Threshold for T cell activation may be a balance between activating signals, such as those delivered by the engagement of CD28 by B7-1 and B7-2, and inhibitory signals, mediated by engagement of PD-1 by PD-L1 and PD-L2. The structural conservation of B7-like and CD28-like receptors may reflect the distance between T cells and APCs in the immunological synapse. The PD-L−PD-1 pathway may play a key role in the induction and/or

PD-L1 and PD-L2 are ligands for PD-1, a costimulatory molecule that plays an inhibitory role in regulating T cell activation in the periphery. PD-L2 also known as PD-L2, B7-DC serves as a negative and a positive regulator of T cell function. The expression and function of PD-L2 are similar to PD-L1. Both PD-L2−PD-1 and PD-L1−PD-1 signals inhibit T cell proliferation by blocking cell cycle progression but not by increasing cell death. PD-L2−PD-1 interactions are able to inhibit TCR-mediated proliferation and cytokine production in the absence of CD28 costimulation. Threshold for T cell activation may be a balance between activating signals, such as those delivered by the engagement of CD28 by B7-1 and B7-2, and inhibitory signals, mediated by engagement of PD-1 by PD-L1 and PD-L2. The structural conservation of B7-like and CD28-like receptors may reflect the distance between T cells and APCs in the immunological synapse. The PD-L−PD-1 pathway may play a key role in the induction and/or

Leukocyte surface antigen CD47 is also known as Antigenic surface determinant protein OA3, Integrin-associated protein (IAP) and Protein MER6. CD47 contains 1 Ig-like V-type (immunoglobulin-like) domain. CD47 is a 40‑60 kDa variably glycosylated atypical member of the immunoglobulin superfamily and an integral membrane protein that consists of a 123 amino acid (aa) extracellular domain (ECD) with a single Ig-like domain, five membrane-spanning regions with short intervening loops, and a 34 aa C-terminal cytoplasmic tail. CD47 has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins and plays an important role in memory formation and synaptic plasticity in the hippocampus by similarity. CD47 is the receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. CD47 Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-

Leukocyte surface antigen CD47 is also known as Antigenic surface determinant protein OA3, Integrin-associated protein (IAP) and Protein MER6. CD47 contains 1 Ig-like V-type (immunoglobulin-like) domain. CD47 is a 40‑60 kDa variably glycosylated atypical member of the immunoglobulin superfamily and an integral membrane protein that consists of a 123 amino acid (aa) extracellular domain (ECD) with a single Ig-like domain, five membrane-spanning regions with short intervening loops, and a 34 aa C-terminal cytoplasmic tail. CD47 has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins and plays an important role in memory formation and synaptic plasticity in the hippocampus by similarity. CD47 is the receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. CD47 Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-

Leukocyte surface antigen CD47 is also known as Antigenic surface determinant protein OA3, Integrin-associated protein (IAP) and Protein MER6. CD47 contains 1 Ig-like V-type (immunoglobulin-like) domain. CD47 is a 40‑60 kDa variably glycosylated atypical member of the immunoglobulin superfamily and an integral membrane protein that consists of a 123 amino acid (aa) extracellular domain (ECD) with a single Ig-like domain, five membrane-spanning regions with short intervening loops, and a 34 aa C-terminal cytoplasmic tail. CD47 has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins and plays an important role in memory formation and synaptic plasticity in the hippocampus by similarity. CD47 is the receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. CD47 Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-