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Cutting Edge: Guillain-Barré Syndrome-Associated IgG Responses to Gangliosides Are Generated Independently of CD1 Function in Mice¹

Yukie Matsumoto^*, Nobuhiro Yuki^2,*, Luc Van Kaer, Koichi Furukawa, Koichi Hirata^* and Masahiko Sugita

^* Department of Neurology and Research Institute for Neuroimmunological Diseases, Dokkyo Medical University School of Medicine, Tochigi, Japan; Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; Department of Biochemistry II, Nagoya University School of Medicine, Nagoya, Japan; and Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan

CD1 molecules present a variety of microbial glycolipids and self-glycolipids to T cells, but their potential role in humoral responses to glycolipid Ags remains to be established. To address this issue directly, we used GM1/GD1a-deficient mice, which, upon immunization with heat-killed Campylobacter jejuni, develop Guillain-Barré syndrome-associated IgG Abs against the GM1/GD1a sugar chain epitopes of bacterial lipo-oligosaccharides (LOS). Our results showed that anti-ganglioside Abs of the IgG1, IgG2b, and IgG3 isotypes were produced in the absence of group 2 CD1 (CD1d) expression. Unlike mouse and human group 2 CD1 molecules that specifically bound LOS, none of the group 1 CD1 molecules (CD1a, CD1b, and CD1c in humans) were capable of interacting with LOS. Thus, these results indicate CD1-independent pathways for anti-ganglioside Ab production.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI 18390263) and the Human Frontier Science Program (RGP0038/2003-C), both to N.Y.

² Address correspondence and reprint requests to Dr. Nobuhiro Yuki, Department of Neurology and Research Institute for Neuroimmunological Diseases, Dokkyo Medical University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi, 321-0293, Japan. E-mail address: yuki-gbs{at}umin.net

³ Abbreviations used in this paper: GBS, Guillain-Barré syndrome; -GC, -galactosylceramide; h, human (prefix); iNKT, invariant NKT; LOS, lipooligosaccharide; TPBS, Tween-PBS.