Dissection of Agonistic and Blocking Effects of CD200 Receptor Antibodies

Abstract

The CD200 receptor (CD200R) is present mainly on myeloid cells and gives inhibitory signals when engaged by its ligand CD200. The interaction is currently of therapeutic interest in cancer and inflammation. However functional effects are complicated by the fact that CD200R is itself polymorphic and also a member of a paired receptor family with four closely related gene products in mice called CD200RLa etc. We show that a second allele of CD200R (termed CD200R(2)) that differs in 7 amino acids also binds CD200 but did not react with the widely used CD200R antibody OX110. Biochemical and functional analysis showed that the CD200/CD200R interaction was blocked by the OX131, mAb that recognises both CD200R(1) and CD200R(2), but not by OX110 mAb. Both mAb can give agonistic inhibitory signals but functional analysis shows OX131 mAb also has the potential to block inhibition by preventing the ligand-receptor interaction and hence gives opposing effects. Although OX131 mAb cross-reacts with the activating receptor CD200RLe, it is specific for CD200R in C57BL/6 whilst OX110 mAb cross-reacts on CD200RLc. The results show the importance of the repertoire of paired receptors in strains or individuals and mAb used with implications for paired receptor analysis and therapeutics.

Signal‐regulatory protein α from the NOD mouse binds human CD47 with an exceptionally high affinity – implications for engraftment of human cells

“…This suggests that the engineering of the NOD SCID mouse with human CD200R may improve the efficacy of grafting. The CD200R does not show the same degree of polymorphism as SIRP α with only two alleles identified that differ in seven amino acids …”

“…The CD200R does not show the same degree of polymorphism as SIRPa with only two alleles identified that differ in seven amino acids. 29 One additional feature in this interaction is that there can be some 'education' of the sensitivity of the SIRPa on macrophages, as indicated by studies on CD47 knockout mice. Hence CD47 À/À red blood cells are removed when injected into wild-type mice but this does not seem to happen in the CD47 À/À mice.…”

Tumor-Derived Vaccines Containing CD200 Inhibit Immune Activation: Implications for Immunotherapy

“…Targeting receptor-ligand interactions has become increasingly important, as indicated by CD200/ CD200 receptor (CD200R) in leukemia cells and CD47/SIRP in many cancers cells [11,[25][26][27]. We developed a peptide inhibitor targeting the CD200R isoform activation receptors [4].…”

A Simple, Versatile Antibody-Based Barcoding Method for Flow Cytometry

“…The identification of eight different immune cell populations using the phenotyping Abs, adapted from a published strategy (23) is shown (Fig. 6b).…”