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Protection of murine systemic lupus by the Ea transgene without expression of I-E heterodimers

Martínez-Soria, Eduardo
Ho, Liza
Published in Journal of Immunology. 2008, vol. 181, no. 5, p. 3651-7
Abstract A high-level expression of the Ea transgene encoding the MHC class II I-E alpha-chain is very effective in the protection from systemic lupus erythematosus (SLE) in mice. However, it has not been elucidated whether this protection results from the induction or increased expression of I-E heterodimers or from the generation of I-E alpha-chain-derived peptides displaying high affinity for I-A molecules, because previous studies were conducted in lupus-prone mice expressing I-E beta-chains. To address this question, we assessed the protective effect of the Ea transgene in lupus-prone BXSB mice bearing the H2(q) haplotype (i.e., unable to express I-E heterodimers because of a deficiency in I-E beta-chains). We observed that the Ea transgene expression resulted in a marked suppression of the development of SLE in H2(q) BXSB mice despite the absence of I-E expression. The observed protection was not associated with any detectable levels of T cell depletion and regulatory T cell expansion. Significantly, transgenic I-E alpha-chains were substantially expressed on the surface of B lymphocytes and dendritic cells, but not of macrophages, without apparent formation of mixed-isotype heterodimers with I-A beta-chains. Our results demonstrate for the first time that the Ea transgene is able to prevent the development of SLE without induction of I-E heterodimer expression, indicating a critical role of I-E alpha-chains, but not I-E heterodimers, in the Ea transgene-mediated protection from SLE. Taken together, our data favor a model of autoimmunity prevention based on competition for Ag presentation between I-E alpha-chain-derived peptides and autoantigens.
Keywords AnimalsAntigen PresentationAutoantigens/metabolismAutoimmunityBinding, CompetitiveDimerizationHistocompatibility Antigens Class II/chemistry/genetics/metabolismLupus Erythematosus, Systemic/immunologyMicePeptide Fragments/immunology/metabolismTransgenes
PMID: 18714040
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Other version: http://www.jimmunol.org/cgi/content/full/181/5/3651
Research groups Groupe Santiago-Raber Marie-Laure (pathologie et immunologie) (915)
Lupus érythémateux systémique, de l'anémie hémolytique et de la glomérulonéphrite (168)
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MARTÍNEZ-SORIA, Eduardo et al. Protection of murine systemic lupus by the Ea transgene without expression of I-E heterodimers. In: Journal of Immunology, 2008, vol. 181, n° 5, p. 3651-7. doi: 10.4049/jimmunol.181.5.3651 https://archive-ouverte.unige.ch/unige:1228

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Deposited on : 2009-03-26

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