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

  • B.-Y. Wei
  • J. Martin
  • S. Savarirayan
  • R. Little
  • C. S. David


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 α k A β b ) 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).


Spleen Cell Mixed Lymphocyte Reaction Double Transgenic Mouse Founder Mouse Tail Skin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Billingham RE, Medawar PB (1951) The technique of free skin grafting in mammals. J Exp Med 28: 235–239.Google Scholar
  2. Blanar MA, Buekly LC, Flavell RA (1989) NF-KB binds within a region required for B-cell specific expression of the major histocompatibility complex class II gene Eαd. Mol Cell Biol 9: 844–846.PubMedGoogle Scholar
  3. Braunstein NS, Germain RN (1987) Allele-specific control of la structure-function relationship. Proc Natl Acad Sci USA 84: 2921–2925.PubMedCrossRefGoogle Scholar
  4. Buerstedde J-M, Pease LR, Nilson AE, Bell MP, Chase C, Buerstedde G, McKean DJ (1988a) Regulation of murine MHC class II molecule expression: Identification of Aß residues resonsible for allele-specific cell surface expression. J Exp Med 168: 823–837.PubMedCrossRefGoogle Scholar
  5. Buerstedde J-M, Pease LR, Nilson MP, Buerstedde G, Murphy D, McKean DJ (1988b) Identification of an immunodominant region on the I-Aß chain using site-directed mutagenesis and DNA-mediated gene transfer. J Exp Med 167: 473–487.PubMedCrossRefGoogle Scholar
  6. Dorn A, Benoist C, Mathis D (1984) New B lymphocyte-specific enhancer-binding protein. Mol Cell Biol 9: 312–320.Google Scholar
  7. Germain RN, Malissen B (1986) Analysis of the expression and function of class II major histocompatibility complex-encoded molecules by DNA-mediated gene transfer. Ann Rev Immunol 4: 281–315.CrossRefGoogle Scholar
  8. Hogan B, Constantini F, Lacy E (1986) Manipulating the mouse embryo: A laboratory Manual. Cold Spring Harbor Laboratory.Google Scholar
  9. Klein J (1986) Natural history of the major histocompatibility complex. John Wiley and Sons, New York.Google Scholar
  10. LeMeur M, Waltzinger C, Gerlinger P, Benoist C, Mathis D (1989) Restricted assembly of MHC class II molecules in transgenic mice. J Immunol 142: 323–327.Google Scholar
  11. Palmiter RD, Brinster RL (1986) Germline transformation of mice. Ann Rev Genet 20: 465–499.PubMedCrossRefGoogle Scholar
  12. Sant AJ, Braunstein HS, Germain RN (1987) Predominant role of amino-terminal sequences in dictating efficiency of class II major histocompatibility complex αß dimer expression. Proc Natl Acad Sci USA 84: 8065–8069.PubMedCrossRefGoogle Scholar
  13. Sen R, Baltimore D (1986) Multiple nuclear factors interact with immunoglobulin enhancer sequences. Cell 46: 705–716.PubMedCrossRefGoogle Scholar
  14. Sullivan KE, Claman AF, Nakamishi M, Tsang SY, Wang Y, Peterlin BM (1987) A model for the transciptional regulation of MHC class II genes. Immunol Today 8: 289–293.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • B.-Y. Wei
  • J. Martin
  • S. Savarirayan
  • R. Little
  • C. S. David
    • 1
  1. 1.Department of ImmunologyMayo ClinicRochesterUSA

Personalised recommendations