H-2 Antigens pp 245-253 | Cite as

Structural and Functional Analysis of Murine Class II Molecules

  • Irwin J. Griffith
  • Laurie H. Glimcher
Part of the NATO ASI Series book series (NSSA, volume 144)


Class II (Ia) major histocompatibility complex (MHC) molecules in the mouse are cell surface glycoproteins expressed on antigen presenting cells (APC; ref. 1). In the mouse two isotypic forms of Ia exist: the I-A and I-E molecules, each a heterodimer composed of noncovalently-associated a and ß chains. The association of foreign antigen, Ia molecules and the clonally distributed antigen receptor on T cells is critical in the initiation and regulation of immune responses1. However, the exact nature of the interaction between T cell receptor, antigen and Ia molecule is still poorly understood at the molecular level.


Major Histocompatibility Complex Immune Response Gene Polymorphic Residue Tertiary Conformation Eell Line 
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. 1.
    R. H. Schwartz, T lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex, Annu. Rev. Immunol. 3: 237 (1985).PubMedCrossRefGoogle Scholar
  2. 2.
    V. Folsom, D. Gay, and S. Tonegawa, The 21 domain of the mouse Eß chain is important for restricted antigen presentation to helper T-cell hybridomas, Proc. Natl. Acad. Sci. USA 82: 1678 (1985).PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    R. N. Germain, J. D. Ashwell, R. I. Lechler, D. H. Margulies, K. M. Nickerson, G. Susuki, and J. Y. L. Tou, “Exon-shuffling” maps control of antibody-and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide Al, Proc. Natl. Acad. Sci. USA 82: 2940 (1985).PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    C. O. Benoist, D. J. Mathis, M. R. Kanter, V. E. Williams II, and H. O. McDevitt, Regions of allelic hypervariability in the murine Aa immune response gene, Cell 34: 169 (1983).PubMedCrossRefGoogle Scholar
  5. 5.
    R. Nairn, K. Yamaga, and S. G. Nathenson, Biochemistry of the gene products from murine MEC mutants, Annu. Rev. Genet. 14: 241 (1980).PubMedCrossRefGoogle Scholar
  6. 6.
    K. R. McIntyre, and J. G. Seidman, Nucleotide sequence of mutant IAzbm12 gene is evidence for genetic exchange between mouse immune response genes, Nature 308: 551 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    L. E. Cohn, L. H. Glimcher, R. A. Waldmann, J. A. Smith, A. Ben-Nun, J. G. Seidman, and E. Choi, Identification of functional regions on the I-Ab molecule by site-directed mutagenesis, Proc. Natl. Acad. Sci. USA 83: 747 (1986).PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    M. A. Brown, L. H. Glimcher, E. A. Nielsen, W. E. Paul, and R. N. Germain, T-cell recognition of Ia molecules selectively altered by a single amino acid substitution, Science 231: 255 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    B. N. Beck, L. H. Glimcher, A. E. Nilson, M. Pierres, and D. J. McKean, The structure-function relationship of I-A molecules: correlation of serologic and functional phenotypes of four I-Ak mutant cell lines, J. Tmmunol. 133: 3176 (1984).Google Scholar
  10. 10.
    H. Quill, R. H. Schwartz, and L. H. Glimcher, Eßk mutant antigen-presenting cell lines expressing altered Aak molecules. J. Immunol. 136: 3351 (1986).PubMedGoogle Scholar
  11. 11.
    P. M. Allen, D. J. McKean, B. N. Beck, J. Sheffield, and L. H. Glimcher, Direct evidence that a class II molecule and a simple globular protein generate multiple determinants, J. Exp Med. 162: 1264 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    I. J. Griffith, E. Choi, and L. H. Glimcher, A single base change in an I-A a-chain alters T-cell recognition. Proc. Natl. Acad. Sci. 84: 1090 (1987).PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    I. J. Griffith, F. M. Carland, and L. H. Glimcher, Alteration of a non-polymorphic residue in a class II Eß gene eliminates an antibody-defined epitope without affecting T cell recognition, J. Immunol. 38: 4480 (1987).Google Scholar
  14. 14.
    L. H. Glimcher, T. Hamano, R. Asofsky, D. H. Sachs, M. Pierres. L. E. Samelson, S. O. Sharrow, and W. E. Paul, I-A mutant functional antigen-presenting cell lines, J. Immunol. 130: 2287 (1983).PubMedGoogle Scholar
  15. 15.
    L. G. Guillet, M.-Z. Lai, T. J. Briner, S. Buus, A. Sette, H. M. Grey, J. A. Smith, M. L. Gefter, Immunological self, nonself discrimination, Science 235: 865 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    R. N. Germain and B. Mallissen, Analysis of the expression and function of class-II major histocompatibility complex-encoded molecules by DNA-mediated gene transfer, Ann. Rev. Immunol. 4: 281 (1986).CrossRefGoogle Scholar
  17. 17.
    D. Landais, H. Matthes, C. Benoist, and D. Mathis, A molecular basis for the Ia.2 and Ia.19 antigenic determinants, Proc. Natl. Acad. Sci. USP 82: 2930 (1985).CrossRefGoogle Scholar
  18. 18.
    D. Larhammar, U. Hammerling, M. Denaro, T. Lund, R. A. Flavell, L. Rask, and P. A. Peterson, Structure of the murine immune response I-Aß locus: sequence of the I-Aß gene and an adjacent ß-chain second domain exon, Cell 34: 179 (1983).PubMedCrossRefGoogle Scholar
  19. 19.
    M. Malissen, T. Hunkapiller, and L. Hood, Nucleotide sequence of a light chain gene of the mouse I-A subregion: Aßd, Science 221: 750 (1983).PubMedCrossRefGoogle Scholar
  20. 20.
    P. Estess, A. B. Begovich, M. Koo, P. P. Jones, and H. O. McDevitt, H.O. Sequence analysis and structure-function correlations of murine q, k, u, s, and f haplotype I-Aß cDNA clones, Proc. Natl. Acad. Sci. USA 83: 3594 (1986).PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    G. Widera, and R. A. Flavell, The nucleotide sequence of the murine IEßb immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex, EMBO J.Google Scholar
  22. 22.
    L. Mengle-Gaw, and H. O. McDevitt, Isolation and characterization of a cDNA clone for the murine I-E0 polypeptide chain, Proc. Natl. Acad. Sci. USA 80: 7621 (1983).PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    H. Saito, R. A. Maki, L. K. Clauton, and S. Tonegawa, Complete primary structures of the Eß chain and gene of the mouse major histocompatibility complex, Proc. Natl, Acad. Sci USA 80: 5520 (1983).CrossRefGoogle Scholar
  24. 24.
    L. Mengle-Gaw, and H. O. McDevitt, Predicted protein sequence of the murine I-Eßs polypeptide chain from CDNA and genomic clones, proc. Natl. Acad. Sci. USA 82: 2910 (1985).PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    L. Mengle-Gaw, and H.O. McDevitt, Allelic variation in the murine la ß chain genes, in: “Regulation of the immune system”, H. Cantor, L. Chess, and E. Sercarz, eds., Alan R. Liss, Inc., NY, (1984).Google Scholar
  26. 26.
    G. G. Schlauder, M. P. Bell, B. N. Beck, A. Nilson, and D. J. McKean, The structure-function relationship of I-A molecules: a biochemical analysis of I-A polypeptides from mutant antigen-presenting cells and evidence of preferential association of allelic forms, J. Tmmunol. 135: 1945 (1985).Google Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Irwin J. Griffith
    • 1
  • Laurie H. Glimcher
    • 1
    • 2
  1. 1.Department of Cancer BiologyHarvard School of Public HealthUSA
  2. 2.Department of MedicineHarvard Medical SchoolBostonUSA

Personalised recommendations