Skip to main content

Advertisement

Log in

Hierarchy in the assembly of HLA-B27 and HLA-Cw3 molecules in transgenic mice

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

Abstract

Cell surface expression of human class I molecules in transgenic mice is dependent upon the available pool of β2-microglobulin (β2m) and the affinity between mouse β2m and human class I molecules. HLA-B27 and HLA-Cw3 transgenes can be expressed in mouse strains of the H-2 haplotypes b,f,k, and s which encode two endogenous class I genes mapping to H-2K and H-2D. The human class I genes cannot be expressed on H-2 dand H-2 qhaplotypes which encode three endogenous class I molecules (K,D,L). This suggests that there may be only enough mouse β2m molecules to support three class I molecules. When both the HLA-B27 and HLA-Cw3 genes are introduced into H-2 bmice, only HLA-Cw3 reaches the cell surface. This suggests that HLA-Cw3 has a higher affinity than HLA-B27 for mouse β2m. The possible implications of our findings regarding the assembly, transport, and expression of class I MHC molecules in vivo are discussed.

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

  • Alexander, J., Payne, J. A., Shigekawa, B., Frelinger, J. A., and Cresswell, P. The transport of class I major histocompatibility complex antigens is determined by sequences in the α1 and α2 protein domains. Immunogenetics 31: 169–178, 1990

    Google Scholar 

  • Allen, H., Fraser, J., Flyer, D., Calvin, S., and Flavell, R. β2-microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db. Proc Natl Acad Sci USA 83: 7447–7451, 1986

    Google Scholar 

  • Arce-Gomerz, B., Jones, E. A., Barnstable, C. J., Solomon, E., and Bodmer W. F. The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for β2-microglobulin. Tissue Antigens 11: 96–112, 1978

    Google Scholar 

  • Bieberich, C., Scangos, G., Tanaka, K., and Jay, G. Regulated expression of a murine class I gene in transgenic mice. Mol Cell Biol 6: 1339–1342, 1986

    Google Scholar 

  • Brodsky, F. M. and Guagliardi, L. E. The cell biology of antigen processing and presentation. Annu Rev Immunol 9: 707–744, 1991

    Google Scholar 

  • Browne, H., Smith, G., Bech, S., and Minsont, S. A complex between the MHC class I homologue encoded by human cytomegalovirus and beta 2 microglobulin. Nature 347: 770–772, 1990

    Google Scholar 

  • Cai, Z. and Pease, L. R. Structural and functional analysis of three D/L-like class I molecules from H-2v: indications of an ancestral family of D/L genes. J Exp Med 175: 583–596, 1992

    Google Scholar 

  • Cox, J. H., Bennink, J. R., and Yewdell, J. W. Retention of adenovirus E19 glycoprotein in the endoplasmic reticulum is essential to its ability to block antigen presentation. J Exp Med 174: 1629–1637, 1991

    Google Scholar 

  • Degan, E., Cohen-Doyle, M. F., and Williams, D. B. Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both β2-microglobulin and peptide. J Exp Med 175: 1653–1661, 1992

    Google Scholar 

  • DeMars, R., Rudersdorf, R., Chang, C., Petersen, J., Strandtmann, J., Korn, N., Sidwell, B., and Orr, H. Mutations that impair a post-transcriptional step in expression of HLA-A and-B antigens. Proc Natl Acad Sci USA 82: 8183–8187, 1985

    Google Scholar 

  • Dill, O., Kievits, F., Koch, S., Ivanyi, P., and Hämmerling, G. J. Immunological function of HLA-C antigens in HLA-Cw3 transgenic mice. Proc Natl Acad Sci USA 85: 5664–5668, 1988

    Google Scholar 

  • Duran, L. W., Horton, R. M., Birschbach, C. W., Chang-Miller, A., and Pease, L. R. Structural relationships among the H-2D-regions of murine MHC haplotypes. J Immunol 142: 288–296, 1989

    Google Scholar 

  • Hedley, M., Forman, J., and Tucker, P. W. D2d, a D-end class I gene: tissue expression and alternative processing of the pre-mRNA. Int Immunol 2: 25–32, 1990

    Google Scholar 

  • Hightower, L. E. Heat shock, stress proteins, chaperones, and proteotoxicity. Cell 66: 191–197, 1991

    Google Scholar 

  • Hosken, N. A. and Bevan, M. J. Defective presentation of endogenous antigen by a cell line expressing class I molecules. Science 248: 367–370, 1990

    Google Scholar 

  • Jefferies, W. A. and Burgert, H. G. HG: E3/19K from adenovirus-2 is an immuno-subversive protein that binds to a structural motif regulating the intracellular transport of major histocompatibility complex class I proteins. J Exp Med 172: 1653–1664, 1990

    Google Scholar 

  • Kalinke, U., Arnold, B. and Hämmerling, G. J. Strong xenogeneic HLA response in transgenic mice after introducing an α3 domain into HLAB27. Nature 348: 642–644, 1990

    Google Scholar 

  • Koller, B. H., Marrack, P., Kappler, J. W., and Smithies, O. Normal development of mice deficient in β2M, MHC class I proteins, and CD8+ T cells. Science 248: 1227–1230, 1990

    Google Scholar 

  • Krangel, M. S., Orr, H. T., and Strominger, J. L. Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell 18: 979–991, 1979

    Google Scholar 

  • Krimpenfort, P., Rudenko, G., Hochstenbach, F., Guessnow, D., Berns, A., and Ploegh, H. Crosses of two independently derived transgenic mice demonstrate functional complementation of the genes encoding heavy (HLA-B27) and light (β2-microglobulin) chains of HLA class I antigens. EMBO J 6: 1673–1676, 1987

    Google Scholar 

  • Lillehoj, E. P., Walsh, W. D., Potter, T., Lee, D. R., Coligan, J. E., and Hansen, T. H. Chemical and serologic definition of two unique D region-encoded molecules in the wild-derived mouse strain B10.GAA37. J Immunol 133: 3138–3142, 1984

    Google Scholar 

  • Ljunggren, H-G and Karre, K. Host resistance directed selectively against H-2-deficient lymphoma variants. J Exp Med 162: 1745–1759, 1985

    Google Scholar 

  • Munro, S. and Pelham, H. R. B. An hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46: 291–300, 1986

    Google Scholar 

  • Neefjes, J. J. and Ploegh, H. L. Allele and locus-specific differences in cell surface expression and the association of HLA class I heavy chain with β2-microglobulin: differential effects of inhibition of glycosylation on class I subunit association. Eur J Immunol 18: 801–810, 1988

    Google Scholar 

  • Neefjes, J. J., Schumacher, T. N. M., and Ploegh, H. L. Assembly and intracellular transport of major histocompatibility complex molecules. Curr Opin Cell Biol 3: 601–609, 1991

    Google Scholar 

  • Nickerson, C. L., Hanson, J., and David, C. S. Expression of HLA-B27 in transgenic mice is dependent on the mouse H-2D genes. J Exp Med 172: 1255–1261, 1990

    Google Scholar 

  • Nickerson-Nutter, C. L., Hogen, K. L., and David, C. S. Expression of HLA-B27 in transgenic mice is controlled by gene(s) mapping between H-2D and H-2L loci. Immunogenetics 35: 199–204, 1992

    Google Scholar 

  • Nuchtern, J. G., Bonifacino, J. S., Biddison, W. E., and Klausner, R. D. Brefeldin A implicates egree from endoplasmic reticulum in class I restricted antigen presentation. Nature 339: 223–226, 1989

    Google Scholar 

  • Owen, M. J., Kissonerghis, A. M., and Lodish, H. F. Biosynthesis of HLA-A and HLA-B antigens in vivo. J Biol Chem 255: 9678–9684, 1980

    Google Scholar 

  • Perarnau, B. M., Gillet, A. C., Hakem, R., Barad, M., and Lemonnier, F. A. Human β2-microglobulin specifically enhances cell-surface expression of HLAclass I molecules in transfected murine cells. J Immunol 141: 1383–1389, 1988

    Google Scholar 

  • Rosa, F., Berissi, H., Weissenbach, J., Maroteaux, L., Fellous, M., and Revel, M. The β2-microglobulin mRNA in human Daudi cells has a mutated initiation codon but is still inducible by interferon. EMBO J 2: 239–243, 1983

    Google Scholar 

  • Sege, L., Rask, L., and Peterson, P. A. Role of β2-microglobulin in the intracellular processing of HLA antigens. Biochemistry 20: 4523–4530, 1981

    Google Scholar 

  • Seong, R. H., Clayberger, C. A., Krensky, A. M., and Parnes, J. R. Rescue of Daudi cell HLA expression by transfection of the mouse β2-microglobulin gene. J Exp Med 167: 288–299, 1988

    Google Scholar 

  • Stephen, D., Sun, H., Fischer Lindahl, K., Myer, E., Hämmerling, G., Hood, L., and Steinmetz, M. Organization and evolution of D region class I genes in the mouse major histocompatibility complex. J Exp Med 163: 1227–1244, 1986

    Google Scholar 

  • Tewarson, S., Figueroa, F., and Klein, J. Identification of D-locus alleles in mouse B10.W lines. Immunogenetics 16: 273–278, 1982

    Google Scholar 

  • Townsend, A., Elliott, T., Cerundolo, V., Foster, L., Barker, B., and Tse, A., Assembly of MHC class I molecules analyzed in vitro. Cell 62: 285–295, 1990

    Google Scholar 

  • Tummuru, U., Zubairu, M. K., and Lee, D. R. The multi-locus H-2D w16region has an organization distinct from the D dregion. Immunogenetics 35: 296–308, 1992

    Google Scholar 

  • Weiss, E. H., Golden, L., Fahrner, K., Mellor, A. L., Devlin, J. J., Bullman, H., Tiddens, H., Bud, H., and Flavell, R. A. Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BI/10 mouse. Nature 310: 650–655, 1984

    Google Scholar 

  • Williams, D. B., Borriello, F., Zeff, R. A., and Nathenson, S. G. Intracellular transport of class I histocompatibility molecules. Influence of protein folding on transport to the cell surface. J Biol Chem 263: 4549–4560, 1988

    Google Scholar 

  • Williams, D. B., Barber, B. H., Flavell, R. A., and Allen, H. Role of β2-microglobulin in the intracellular transport and surface expression of murine class I histocompatibility molecules. J Immunol 142: 2796–2806, 1989

    Google Scholar 

  • Yewdell, J. W. and Bennick, J. R. Brefeldin A specifically inhibits presentation of protein antigens to cytotoxic T lymphocytes. Science 244: 1072–1075, 1989

    Google Scholar 

  • Zemmour, J. and Parham, P. Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C. J Exp Med 176: 937–950, 1992

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pedrinaci, S., Hanson, J. & David, C. Hierarchy in the assembly of HLA-B27 and HLA-Cw3 molecules in transgenic mice. Immunogenetics 39, 130–137 (1994). https://doi.org/10.1007/BF00188616

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00188616

Keywords

Navigation