SIRP family of immune checkpoint proteins

SIRPs are paired receptors, with similar extracellular domains but different transmembrane and cytoplasmic regions which result in opposing signals, either activating or inhibitory. The best studied SIRP family member is SIRP alpha. SIRP alpha expression is restricted to myeloid cells while its binding partner CD47 is expressed on T cells. Reagents blocking the SIRP-alpha/CD47 interaction could activate macrophages or dendritic cells to stimulate phagocytosis and to eliminate tumor cells. Preclinical studies have suggested that SIRP alpha or CD47 blockade may have synergistic antitumor effects in combination with other immune checkpoint inhibitors that target the adaptive immune system. SIRP gamma also binds to CD47, albeit with lower affinity than SIRP alpha. While a SIRP beta ligand remains unknown, SIRP beta has been shown to associate with the adaptor protein DAP12 via a basic amino acid motif in its cytoplasmic region leading to activation phagocytosis by macrophages.

SIRP alpha bioactivity QC testing

Biotinylated and Unlabeled Human SIRP α Support the Adhesion of Red Blood Cells. Red blood cells from human whole blood were incubated with the indicated concentrations of immobilized Recombinant Human SIRPα/CD172a Fc (Catalog # 4546-SA) or Biotinylated Recombinant Human SIRPα/CD172a Fc (Catalog # BT4546). The similarity in activity highlights that biotinylation does not affect the specificity.

Recombinant Human SIRP alpha Binds the Receptor CD47 in an ELISA Binding Assay. When Recombinant Human SIRP alpha /CD172a His-tag (Catalog # 9378-SA) is coated at 0.5 μg/mL, 100 μL/well, Recombinant Human CD47 Fc Chimera (Catalog # 4670-CD) binds with an ED50 of 0.04-0.24 μg/mL.

Recombinant Mouse SIRP alpha Activity is Suppressed by a Soluble Version of the CD47 Receptor. Mouse red blood cells incubated with Mouse SIRP alpha Fc (Catalog # 7154-SA) promotes cell adhesion (green line). When Recombinant Mouse SIRP alpha Fc is immobilized at 2 µg/mL, cell adhesion can be antagonized by the addition of soluble Recombinant Mouse CD47 Fc (Catalog # 1866-CD; blue line).

View other Immune-checkpoint blockade targets

• Butyrophilins
• AMIGOs
• LILRA/B Receptors
• B7/CD28 Family
• CEACAM
• VSIG
• VSTM

Related Pathways

T Cell Co-Signaling Pathway: Ligand-Receptor Interactions

Mechanisms of Regulatory T Cell-Mediated Suppression

Other immune-checkpoint blockade resources:

• Current and Emerging Immune Checkpoint Targets for Immuno-Oncology Research eBook
• Immune Checkpoint
• Immune Checkpoint Blockade: Immune Checkpoint Molecule Expression
• Immune Checkpoint Blockade: Immune Cell Phenotyping and Isolation
• Immune Checkpoint Blockade: T Cell Responses
• VSIG8 Poster: Co-inhibitory Immune Checkpoint Molecule
• Webinar Short: B7-related Butryophilins as Immune Modulators
• Immunotherapy
• A Role for VSIG-3/VISTA Signaling in Acquired Resistance to Anti-PD-1 Therapy?

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