EPSTEIN-BARR-VIRUS COMPLEMENT C3D RECEPTOR IS AN INTERFERON-ALPHA RECEPTOR

Interferon-alpha contains a sequence motif similar to the complement receptor type two (CR2/CD21) binding site on complement fragment C3d. Antibodies against a peptide with the CR2 binding sequence on C3d react with a peptide carrying the IFN-alpha CR2 binding motif (residues 92-99) and with recombinant IFN-alpha. The IFN-alpha-derived peptide, as well as recombinant IFN-alpha, inhibits C3bi/C3d interaction with CR2 on the Burkitt lymphoma Raji. The direct interaction of IFN-alpha and CR2 is inhibited by polyclonal anti-IFN-alpha, anti-CR2 and anti-C3d peptide antibodies as well as by C3bi/C3d, EBV coat protein gp350/220 and IFN but not by IFN-gamma. [I-125]IFN-alpha binding to Raji cells is inhibited by polyclonal anti-IFN-alpha and anti-CR2 antibodies, by peptides with the CR2 binding motif and partially by C3bi/C3d. Monoclonal anti-CR2 antibody HB5, but not OKB-7, blocks IFN-alpha binding to Raji cells. CR2 or CR2-like molecules may therefore be the major IFN-alpha receptors on B lymphocytes.