Induction of autoantibodies to mouse CCR5 with recombinant papillomavirus particles.
The vertebrate immune system has evolved to respond vigorously to microbial infection but to ignore self-antigens. Evidence has emerged that B cell responses to viruses are initiated by immune recognition of ordered arrays of antigen on the viral surface. To test whether autoantibodies against a self-antigen can be induced by placing it in a context that mimics the ordered surface of a viral particle, a peptide representing an extracellular loop of the mouse chemokine receptor CCR5 was incorporated into an immunodominant site of the bovine papillomavirus virus L1 coat protein, which self-assembles into virus-like particles. Mice inoculated with chimeric L1-CCR5 particles generated autoantibodies that bound to native mouse CCR5, inhibited binding of its ligand RANTES, and blocked HIV-1 infection of an indicator cell line expressing a human-mouse CCR5 chimera. These results suggest a general method for inducing autoantibodies against self-antigens, with diverse potential basic research and clinical applications.
Chackerian
B
B
Laboratory of Cellular Oncology, National Institutes of Health, Building 36, Room 1D-32, Bethesda, MD 20892-4040, USA.
Lowy
D R
DR
Schiller
J T
JT
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D052688:Bovine papillomavirus 1 / Q000235:genetics; D002213:Capsid / Q000235:genetics / Q000276:immunology; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D019713:Receptors, CCR5 / Q000737:chemistry / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D019713:Receptors, CCR5; D011993:Recombinant Fusion Proteins