Prevention of murine lupus by an I-E α chain transgene: Protective role of I-E α chain-derived peptides with a high affinity to I-Ab molecules

Autor: Shozo Izui, Nabila Ibnou-Zekri, Kimi Araki, Masahiro Iwamoto
Rok vydání: 1996
Předmět:
Male
Genetically modified mouse
medicine.medical_specialty
Ovalbumin
Transgene
Molecular Sequence Data
Immunology
Antigen presentation
Gene Dosage
Alpha (ethology)
Mice
Transgenic
ddc:616.07
Biology
Major histocompatibility complex
medicine.disease_cause
Autoimmunity
Mice
Immune system
Transgenes/ immunology
immune system diseases
Internal medicine
medicine
Lupus Erythematosus
Systemic
Animals
Immunology and Allergy
Transgenes
Amino Acid Sequence
skin and connective tissue diseases
Crosses
Genetic
Protein Binding/immunology
Histocompatibility Antigens Class II
Molecular biology
Ovalbumin/immunology
Endocrinology
Peptides/chemistry/ immunology
Radiation Chimera
Histocompatibility Antigens Class II/ chemistry/ genetics/therapeutic use
biology.protein
Female
Lupus Erythematosus
Systemic/ genetics/immunology/ prevention & control
Radiation Chimera/immunology
Peptides
Alpha chain
Protein Binding
Zdroj: European Journal of Immunology, Vol. 26, No 2 (1996) pp. 307-314
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.1830260206
Popis: 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.
Databáze: OpenAIRE
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