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Title

Prevention of murine lupus by an I-E alpha chain transgene: protective role of I-E alpha chain-derived peptides with a high affinity to I-Ab molecules
Authors
Iwamoto, Masahiro
Ibnou-Zekri, Nabila
Araki, Kimi
Izui, Shozo
Published in European Journal of Immunology. 1996, vol. 26, no. 2, p. 307-314
Abstract The expression of a transgene encoding the I-E alpha chain prevents a lupus-like autoimmune syndrome in BXSB mice. However, it had not been elucidated whether the E alpha d transgene-mediated protective effect results from I-E expression or from the generation of I-E alpha chain-derived peptides (E alpha peptide) displaying high affinity for the I-Ab molecule. To address this question, two different BXSB lines expressing the transgene at low or high levels were crossed with lupus-prone MRL mice; this resulted in three types of (MRL x BXSB)F1 mice, differing in the expression levels of I-E molecules and of E alpha peptides presented by I-Ab molecules. Comparative analysis of these three (MRL x BXSB)F1 mice as well as several BXSB transgenic lines showed that the E alpha d transgene-mediated protection paralleled the expression levels of E alpha peptide presented by I-Ab molecules, but not of I-E molecules on B cells. In addition, use of transgenic and nontransgenic double bone marrow chimeras showed a selective activation of nontransgenic B cells during I-Ab-restricted T cell-dependent immune responses, while both transgenic and nontransgenic B cells were comparably activated during T cell-independent responses. These results favor a model of autoimmunity prevention based on competition for antigen presentation, in which excessive generation of E alpha peptides prevents, because of their high affinity to the I-A molecules, activation of potential autoreactive T and B cells.
Keywords Amino Acid Sequence — Animals — Crosses, Genetic — Female — Gene Dosage — Histocompatibility Antigens Class II/ chemistry/ genetics/therapeutic use — Lupus Erythematosus, Systemic/ genetics/immunology/ prevention & control — Male — Mice — Mice, Transgenic — Molecular Sequence Data — Ovalbumin/immunology — Peptides/chemistry/ immunology — Protein Binding/immunology — Radiation Chimera/immunology — Transgenes/ immunology
Identifiers
PMID: 8617296
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(ISO format) 		IWAMOTO, Masahiro et al. Prevention of murine lupus by an I-E alpha chain transgene: protective role of I-E alpha chain-derived peptides with a high affinity to I-Ab molecules. In: European Journal of Immunology, 1996, vol. 26, n° 2, p. 307-314. doi: 10.1002/eji.1830260206 https://archive-ouverte.unige.ch/unige:11336

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Deposited on : 2010-08-27

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