Cutting edge: FcR-like 6 is an MHC class II receptor.
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.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Daniel M
DM
Schreeder
John P
JP
Cannon
Jiongru
J
Wu
Ran
R
Li
Mikhail A
MA
Shakhmatov
Randall S
RS
Davis
D000328:Adult; D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D005810:Multigene Family / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; C520037:FCRL6 protein, human; D006684:HLA-DR Antigens; D008024:Ligands; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins