caa a22 4500 467907005 CHVBK 20180406152837.0 cr unu---uuuuu 170328e20060401xx s 000 0 eng 10.1007/s00251-006-0100-y doi (NATIONALLICENCE)springer-10.1007/s00251-006-0100-y Restrictive and diversifying elements of the anti-myelin/oligodendrocyte glycoprotein antibody response in primate experimental allergic encephalomyelitis [Elektronische Daten] [H.-Christian von Büdingen, Til Menge, Stephen Hauser, Claude Genain] Autoantibody responses against conformational epitopes of myelin/oligodendrocyte glycoprotein (MOG) possess myelin destructive potential, as demonstrated in the marmoset model of human multiple sclerosis (MS) and in some rodent models of experimental allergic encephalomyelitis. We have previously characterized monoclonal Fab fragments specific for conformational epitopes of MOG that were derived from a combinatorial antibody library generated from a MOG-immune marmoset. In this paper, we address the molecular heterogeneity of humoral responses against MOG in this outbred model of MS by studying additional antibody clones derived from a genetically unrelated animal. We find that all MOG-specific IgGκ Fab fragments, unrelated to genetic make-up, utilize a restricted set of variable region genes, IGHV1 and IGHV3 for the H chain and IGKV1, IGKV3, and IGKV5 for the L chain. Despite these restricting factors, diversity within these antibody repertoires can be observed, predominantly within the H-chain CDR3 regions. Our findings suggest that only a limited set of Ig genes is necessary to launch a diverse, destructive humoral immune response against a single CNS antigen in primates. These results are the first to contribute to a better understanding of how myelin-directed and potentially destructive autoantibody responses may develop in human MS. Springer-Verlag, 2006 Experimental allergic encephalomyelitis nationallicence Multiple sclerosis nationallicence Myelin-oligodendrocyte glycoprotein nationallicence Autoantibodies nationallicence Immunoglobulin genes nationallicence von Büdingen H.-Christian Department of Neurology, University Hospital Zürich, 8091, Zürich, Switzerland aut Menge Til Department of Neurology, University of California School of Medicine, 505 Parnassus Avenue, 94143-0114, San Francisco, CA, USA aut Hauser Stephen Department of Neurology, University of California School of Medicine, 505 Parnassus Avenue, 94143-0114, San Francisco, CA, USA aut Genain Claude Department of Neurology, University of California School of Medicine, 505 Parnassus Avenue, 94143-0114, San Francisco, CA, USA aut Immunogenetics Springer-Verlag 58/2-3(2006-04-01), 122-128 0093-7711 58:2-3<122 2006 58 251 https://doi.org/10.1007/s00251-006-0100-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-006-0100-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- von Büdingen H.-Christian Department of Neurology, University Hospital Zürich, 8091, Zürich, Switzerland aut NATIONALLICENCE 700 1- Menge Til Department of Neurology, University of California School of Medicine, 505 Parnassus Avenue, 94143-0114, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Hauser Stephen Department of Neurology, University of California School of Medicine, 505 Parnassus Avenue, 94143-0114, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Genain Claude Department of Neurology, University of California School of Medicine, 505 Parnassus Avenue, 94143-0114, San Francisco, CA, USA aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 58/2-3(2006-04-01), 122-128 0093-7711 58:2-3<122 2006 58 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer