Skip to main content
Log in

Charactreization of polymorphism within the H-2M MHC class II loci

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The products of the class II-like H2-M genes of the major histocompatibility complex are required for class II antigen processing. We sequenced H2-Ma and Mb from several mouse strains to determine whether these genes are polymophic, like H2-O. Both Mb loci appear to be transcribed and are distinct from each other. Mb1 and Mb2 differ by about 11% at the nucleotide level and are most dissimilar in their second exons (corresponding to the β1 domain). Relative to the published Mb 1 d haplotype sequence, the products of the b, g7, f, and k2 alleles of Mb 1 from Mus musculus domesticus and the separate mouse species Mus spretus differ by only one to four amino acids. The majority of the changes occured in the second exon of Mb 1, in contrast to HLA-DMB, the human orthologue. Little polymorphism was seen for Mb 2, and Ma was invariant in all strians tested. The similarity of the g7 allele to those from other haplotypes makes it unlikely that the M class II genes play a role in the autoimmune diabetes of NOD strain mice. The M genes are regulated in a manner similar to classical class II genes, in that they are upregulated by IFN-gd in mcrophages, and to a lesser extend by IL4 in B cells. When modeled on the crystal structure of the HLA-DR1 class II molecule, nearly all of the differences between Mβ1 and Mβ2 affect residues facing away from the putative peptide binding groove.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Avva, R. R. and Cresswell, P. In vivo and in vitro formation and dissociation og HLA-DR complexes with variant chain-derived peptides. Immunity 1: 763–774, 1994

    Google Scholar 

  • Brooks, A. G., Campbell, P. L., Reynolds, P., Gautam, A. M., and McCluskey, J. Antigen presentation and assembly the mouse I-Aκ class II molecules in human APC containing deleted or mutated HLA DM genes. J Immunol 153: 5382–5392, 1994

    Google Scholar 

  • Brown, J. H., Jardetzky, T. S., Gorgan, J. C., Stern, L. J., Urban, R. G., Strominger, J. L., and Wiley, D. C. Three-dimsensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364: 33–39, 1993

    Article  CAS  PubMed  Google Scholar 

  • Carrington, M. and Harding, A. Sequence analysis of two novel HLA-DMA alleles. Immunogenetics 40: 165, 1994

    Google Scholar 

  • Castellino, F. and germain, R. Extensive trafficking of MHC claa II-invariant chain complexes in the endocytic pathway and appearance of peptide-loaded class II in multiple compartment. Immunity 2: 73–88, 1995

    Google Scholar 

  • Ceman, S., Rudesdorf, R., Long, E. O., and Demars, R. MHC class II deletion muatnt expresses normal levels of transgene encoded class II molecules that have abnormal comformation and impaired antigen presentation ability. J Immunol 149: 754–761, 1992

    Google Scholar 

  • Cho, S., Attaya, M., Brown, M. G., and Monaco, J. J. A cluster of transcribed sequences between the Pb and Ob of the murine major histocompatibility complex. Proc Natl Acad Sci USA 88: 5197–5201, 1991 b

    Google Scholar 

  • Chomczynsky, P. and Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159, 1987

    Article  CAS  PubMed  Google Scholar 

  • Cresswell, P. Assembly, transport, and function of MHC class II molecules. Annu Rev Immunol 12: 259–293, 1994

    Google Scholar 

  • Denzin, L. K., Robbins, N. F., Carboy-Newcomb, C., and Cresswell, P. Assembly and intracellular transport of HLA-DM and correction of the class II antigen-processing defect in T2 cells. Immunity 1: 1–20, 1994

    Google Scholar 

  • Diment, S. and Shinde, S. Selective processing of exogenous antigens by antigen-presenting cells with deleted MHC genes. J Immunol 154: 530–535, 1995

    Google Scholar 

  • Estess, P., Begovich, A. B., Koo, M., Jones, p. P., and McDevitt, H. O. Sequence analysis and structure-function correlates of murine q, k, u, s, and f haplotype I-Aβ cDNA clones. Proc Natl Acad Sci USA 83: 3594–3598, 1986

    Google Scholar 

  • Fling, S. P., Arpn, B., and Pious, D. HLA-DMA and-DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells. Nature 368: 554–558, 1994

    Google Scholar 

  • Gorski, J. and Mach, B. Polymorphism of human I a antigens: gene conversion between tow DR β loci results in a new HLA-D/DR specificity. Nature 322: 67–70, 1986

    Google Scholar 

  • Harding, C. V. and Geuze, H. J. Immunogenic peptides bind to MHC class II molecules in an early lysosomal compartment. J Immunol 151: 3988–3998, 1993

    Google Scholar 

  • Jones, P. P., Begovich, A. B., Tacchini-Cottier, F. M., and Vu, T. H. Evolution of class II genes: role of selection in both maintainance of polymorphism and the retention of non-expressed alleles. Immunol Res 9: 200–211, 1990

    Google Scholar 

  • Kralsoon, L., Péléraux, A. Lidstedt, R., Liljedahl, M. Peterson, P. Reconstitution of an operational MHC class II compartment in nonantigen-presenting cells. Science: 1569–1573, 1994

  • Kelly, A. P., Monaco, J. J., Cho, S., and Towsdale, J. A new human HLA class II-related locus, DM. Nature 353: 571–573, 1991

    Google Scholar 

  • King, D. P. and Jones, P. P. Induction of Ia and H-2 antigens on a macrpohage cell line by immune interferon. J Immunol 131: 315–318, 1983

    Google Scholar 

  • Klein, J. History of the Major Histocompatibility Complex, Wiley, New York, 1986

    Google Scholar 

  • McConnell, T. J., Talbot, W. S., McIndoe, R. A., and Wakeland, E. K. The origin of MHC class II gene polymorphism withim the genus Mus. Nature 332: 651–654, 1988

    CAS  PubMed  Google Scholar 

  • Mellins, E., Kempin, S., Smith, L., Monji, T., and Pious, D. A. A gene required for class II antigen presentation maps to the major histocompatibility complex. J Exp Med 174: 1607–1615, 1991

    Google Scholar 

  • Mellins, E., Smith, L., Arp, B., Conter, T., Celis, E., and Pious, D. Defective processing and presentation of exogenous antigens in muatnts with normal HLA class II genes. Nature 343: 71–74, 1990

    Google Scholar 

  • Mengle-Gaw, L., Conner, S., McDevitt, H. C., and Farthman, C. G. Gene conversion between murine class II major histocompatibility complex loci. J Exp Med 160: 1184–1194, 1984

    Google Scholar 

  • Morris, P., Shaman, J., Attaya, M., Amaya, M., Goodman, S., Bergman, C., Monaco, J. J., and Mellins, E. An essential role for HLA-DM inatigen presentation by class II major histocompatibility molecules. Nature 368: 551–554, 1994

    Google Scholar 

  • Nathenson, S. G., Geliebter, J., Pfaffenbach, G. M., and Zeff, R. A. Murine major histocompatibility complex class-I mutants: molecular analysis and strcuture function relationships. Annu Rev Immunol 4: 471–502, 1986

    Google Scholar 

  • Nauss, J. L., Reid, R. H., and Sadegh-Nasseri, S. Accuracy structural homology model for the DR1 class II MHC molecule: comparison to the crystal structure. J Biochem Structure Dyn in press, 1994

  • Pease, L. R., Schulze, D. H., Pfaffenbach, G. M., and Nathenson, S. G. Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex. Proc Natl Acad Sci USA 80: 242–246, 1983

    Google Scholar 

  • Riberdy, J. M. and Cresswell, P. The antigen-processing mutant T2 suggests a role for MHC-linked genes in class II antigen presentation. J Immunol 148: 2586–2590, 1992

    Google Scholar 

  • Riberdy, J. M., Newcomb, J. R., Surman, m. J., Barbosa, J. A., and Cresswell, P. HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides. Nature 360: 474–476, 1992

    Google Scholar 

  • Riberdy, J. M, Avva, R. R., geuze, H. J., and Cresswell, P. Transport and intracellular distribution of MHC class II molecules and associated variant chain in normal and antigen-processing mutant cell lines. J Cell Biol 125: 1225–1237, 1994

    Google Scholar 

  • Saiki, R. K., Gelfand, D. H., Stoeffel, S., Scharf, S. J., Higuchi, R., Horn, G. T., Mullis, K. B., and Erlich, H. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239: 487–491, 1988

    CAS  PubMed  Google Scholar 

  • Sanderson, F., Powis, S. H., Kelly, A. P., and Trowsdale, J. Limited polymorphism in HLA-DM does not involeve the peptide binding groove. Immunogenetics 39: 56–58, 1994a

    Google Scholar 

  • Sanderson, F., Kleijmmer, M., Kelly, A., Verwoerd, D., Tulp, A., Neefjes, J. J., Geuze, H. J., and Trowsdale, J. Accumulation of HLA-DM, a regulator of antigen presentation, in MHC class II compartments. Science 266: 1566–1569, 1994b

    Google Scholar 

  • Sanger, F., Nicklen, S., and Coulson, A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977

    CAS  PubMed  Google Scholar 

  • Sette, A., Ceman, S., Kubo, R. T., Sakaguchi, K, Appella, E., Hunt, D. F., Davis, T. A., Michel, H., Shabanowitz, J., Rudersdorf, R., Grey, H. M., and DeMars, R. Invariant chain peptides in most HLA-DR molecules of an antigen-processing mutants. Science 258: 1801–1804, 1992

    Google Scholar 

  • She, J. X., Boehme, S. A., Wang, T. W., Bonhomme, F., and Wakeland, E. K. Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination. Proc Natl Acad Sci USA 88: 453–457, 1991

    Google Scholar 

  • Stebbins, C. C., Loss, G. E., Elias, C. G., Chervonsky, A., and Sant, A. J. The requierement for DM in class II-restricted antigen presentation and SDS-stable dimer formation is allele and species dependent. J Exp Med 183: 223–2234, 1995

    Google Scholar 

  • Stern, L. J., Brown, J. H., Jaretzky, T. S., Gorga, J. C., Urban, R. G., Strominger, J. L., and Wiley, D. C. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 368: 215–221, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hermel, E., Yuan, J. & Monaco, J.J. Charactreization of polymorphism within the H-2M MHC class II loci. Immunogenetics 42, 136–142 (1995). https://doi.org/10.1007/BF00178588

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00178588

Keywords

Navigation