Cutting edge: FcR-like 6 is an MHC class II receptor

• Published in: The Journal of immunology (1950) Vol. 185; no. 1; pp. 23 - 27
• Main Authors: Schreeder, Daniel M, Cannon, John P, Wu, Jiongru, Li, Ran, Shakhmatov, Mikhail A, Davis, Randall S
• Format: Journal Article
• Language: English
• Published: United States 01.07.2010
• Subjects: Adult; Animals; Antibodies, Blocking - metabolism; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Cell Line; Cell Line, Tumor; Coculture Techniques; HLA-DR Antigens - genetics; HLA-DR Antigens - immunology; HLA-DR Antigens - metabolism; Humans; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Ligands; Mice; Mice, Inbred BALB C; Multigene Family - immunology; Protein Binding - genetics; Protein Binding - immunology; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; Receptors, Fc - genetics; Receptors, Fc - immunology; Receptors, Fc - metabolism; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Recombinant Fusion Proteins - physiology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000832

Receptors for the Fc portion of Ig have been extensively characterized and are known to regulate humoral responses, but members of the closely related FcR-like (FCRL) family have not been found to bind Ig, and to date, no ligand has been identified for any FCRL. Using a cell-based GFP reporter system and a recombinant Fc chimeric protein, we show that human FCRL6, a receptor selectively expressed by cytotoxic T and NK cells, directly binds HLA-DR, an MHC class II molecule. Given the similarity among constant regions of Ig and MHC molecules, these findings suggest that representatives of the FcR and FCRL multigene families may have independently evolved to engage two ancestral elements fundamental to adaptive immunity. This discovery may offer new insight into the interaction between cytotoxic lymphocytes and APCs and may have important implications for better understanding HLA disease susceptibility and pathogenesis.