Abstract
Class II major histocompatibility molecules, or la antigens, are restriction elements for the regulation of immune response. Ia antigens also play a crucial role in the induction of immune tolerance, as well as in the susceptibility to certain diseases. The murine Ia molecules consist of A and E heterodimers, each composed of an α and a β polypeptide, both of which exhibit high degree of polymorphism. Sequence analysis of allelic Aα and Aβ chain revealed that most polymorphic residues are located in the N-terminal of αl and β1 domains (Klein, 1986). These polymorphic residues may not only decide the binding of peptide, but also determine the pairing between α and β chains (Braunstein and Germain, 1987; Buerstedde, Pease, Nilson, Bell, Chase, Buerstedde and McKean, 1988a). Analyses of L cell and B lymphoma cell transfected with different α and ß alleles have indicated that Aα and Aβ chain did not associate freely to form heterodimer on the cell surface. Haplotype-matched hα:hβ pairs gave high level of expression in transfected cells. Some haplotype-mismatched combinations (e.g. A kα A bβ ) can be expressed on the cell surface, while other combinations were not detected (Germain and Malissen, 1986). Studies using hybrid gene constructs suggest that amino acid sequence in the N-terminal half of the β1 domain is responsible for the pairing defects of these α/β chain combinations (Sant, Braunstein and Germain, 1987; Buerstedde, Pease, Nilson, Bell, Chase, Buerstedde and McKean, 1988a).
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© 1990 Springer-Verlag Berlin Heidelberg
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Wei, BY., Martin, J., Savarirayan, S., Little, R., David, C.S. (1990). Transgenic Mice with MHC Class II Genes: The Use in the Study of Allelic α/β Chain Pairing and the Production of Engineered Mice with Mutant I-A Genes. In: Egorov, I.K., David, C.S. (eds) Transgenic Mice and Mutants in MHC Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75442-5_32
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DOI: https://doi.org/10.1007/978-3-642-75442-5_32
Publisher Name: Springer, Berlin, Heidelberg
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