C-C chemokine receptor type 1 (CCR1), C-C chemokine receptor type 3 (CCR3), and C-C chemokine receptor type 5 (CCR5) (CCR1/CCR3/CCR5)

The C-C chemokine receptors CCR1, CCR3, and CCR5 are G protein-coupled receptors (GPCRs) predominantly expressed on professional antigen-presenting cells (APCs), including dendritic cells and macrophages [2, 4]. These receptors are the natural targets for the chemokine MIP-1α (CCL3) and its potent human isoform LD78β (CCL3L1), which regulate immune cell trafficking and activation [3]. In therapeutic development, these receptors are utilized as specific "docking sites" for fusion proteins or DNA vaccines (e.g., the Vaccibody platform) that incorporate LD78β to deliver antigens directly to APCs [1, 5]. This targeted approach facilitates efficient receptor-mediated endocytosis, leading to superior antigen processing and MHC class I/II presentation, which significantly boosts CD8+ and CD4+ T-cell responses [2, 5]. These receptors are also involved in the pathogenesis of various diseases; for instance, CCR5 is a well-known co-receptor for HIV-1 entry [4]. Therapeutic candidates like VB10.16 target these receptors to treat HPV-16-induced malignancies, while small molecules like Maraviroc act as antagonists to block viral entry or inflammatory signaling [1, 4]. Sources: [1] Nykode Therapeutics. "The Vaccibody™ technology." (2024). [2] Gudmundsdotter, L., et al. "Targeting of antigens to chemokine receptors on mice and human professional antigen-presenting cells." Vaccine (2011). [3] Menten, P., et al. "The human CC chemokine LD78β is a potent inhibitor of HIV-1." Journal of Clinical Investigation (1999). [4] Oppermann, M. "Chemokine receptor CCR5: insights into structure, function, and disease." Cellular Signalling (2004). [5] Grødeland, G., et al. "Targeting of Antigen to Antigen-Presenting Cells." Frontiers in Immunology (2020).

Other names

MIP-1 alpha receptorsLD78 beta receptorsAPC chemokine receptorsCCL3 receptorsCCL3L1 receptorsAntigen-presenting cell chemokine receptors

Targeted delivery of antigens to antigen-presenting cells via chemokine receptor-mediated endocytosis to enhance T-cell activation.