Restrictive and diversifying elements of the anti-myelin/oligodendrocyte glycoprotein antibody response in primate experimental allergic encephalomyelitis

Immunogenetics
H-Christian von BüdingenClaude P Genain

Abstract

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 IgGkappa 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 be...Continue Reading

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Citations

Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathali KaushanskyAvraham Ben-Nun
Jun 6, 2017·Journal of Neuroscience Research·Heather YongJacqueline Quandt

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