CD200 receptor-like protein a (CD200RLa)

CD200 receptor-like protein a (CD200RLa) is a cell surface glycoprotein belonging to the immunoglobulin superfamily, primarily characterized in non-human primates such as the cynomolgus macaque. While the closely related CD200R1 receptor provides inhibitory signals to the immune system, CD200RLa serves as an activating counterpart that signals through the DAP12 adapter protein. This receptor is of significant interest in biotechnology and drug development as a "counter-target" or safety target; antibodies designed to agonize the inhibitory CD200R1 pathway must be screened for cross-reactivity with CD200RLa to avoid unintended immune activation. Off-target binding to CD200RLa can lead to adverse effects such as mast cell degranulation and the release of pro-inflammatory cytokines, which complicates the therapeutic window for immunomodulatory drugs. Consequently, understanding the expression and functional profile of CD200RLa is essential for ensuring the safety and selectivity of therapies targeting the CD200-CD200R axis in inflammatory and oncological diseases.

Other names

CD200 receptor 2CD200 receptor 1-likeCD200R2CD200R1LCynomolgus CD200RLaActivating CD200 receptor

CD200RLa functions as an activating receptor by associating with the DAP12 (DNAX activating protein 12) adapter molecule, which contains immunoreceptor tyrosine-based activation motifs (ITAMs). Upon binding to its ligand (CD200) or through antibody-mediated cross-linking, it triggers a signaling cascade that leads to the activation of myeloid cells, such as mast cells and macrophages, resulting in the release of pro-inflammatory cytokines and mediators.