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Dissection of agonistic and blocking effects of CD200 receptor antibodies
Munir Akkaya1, Marie-Laure Aknin, Billur Akkaya
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom.
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.
Insights
The CD200 receptor (CD200R) has different forms, including CD200R(2), which binds CD200 but is not detected by the OX110 antibody. This discovery impacts cancer and inflammation therapies.
Area of Science:
- Immunology
- Molecular Biology
Background:
- The CD200 receptor (CD200R) on myeloid cells mediates inhibitory signals upon binding its ligand, CD200.
- CD200R signaling is therapeutically relevant for cancer and inflammation but complicated by receptor polymorphism and its paired receptor family members.
Purpose of the Study:
- To investigate the functional consequences of CD200 receptor polymorphism.
- To characterize a newly identified CD200R allele, CD200R(2), and its interaction with CD200.
- To evaluate the specificity and function of CD200R antibodies (OX110 and OX131).
Main Methods:
- Biochemical and functional analyses of CD200/CD200R interactions.
- Utilized monoclonal antibodies (mAbs) OX110 and OX131 for binding and functional assays.
- Investigated cross-reactivity with related paired receptors (CD200RLe, CD200RLc).
Main Results:
- A novel CD200R allele, CD200R(2), was identified, differing by 7 amino acids and binding CD200.
- The OX110 mAb did not recognize CD200R(2), while OX131 mAb recognized both CD200R(1) and CD200R(2).
- OX131 mAb blocked CD200/CD200R interaction, exhibiting both agonistic and antagonistic effects, unlike OX110 mAb.
Conclusions:
- The study highlights the importance of CD200 receptor repertoire diversity in different individuals or strains.
- Antibody specificity is critical for accurate paired receptor analysis and therapeutic applications.
- Understanding CD200R polymorphism and antibody interactions is crucial for developing targeted immunotherapies.
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