Skip to main content
Log in

Polymorphism and complexity of HLA-DR: evidence for intra-HLA-DR region crossing-over events

  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

HLA-DR molecules were isolated from HLA-DR3, −5, and −w6 positive homozygous B-cell lines by immunoprecipitation with monoclonal antibodies and analyzed by gel electrophoretic techniques. DNA isolated from the same cell lines was digested with the restriction enzyme Taq I and hybridized with a DR beta full-length cDNA probe. We demonstrated that certain DR βI alleles are found in combination with different DR βIII alleles as defined by Southern blotting, protein chemistry, a functional assay using purified protein derivative-specific T-cell lines, and, in one case, also alloreactive T-cell reagents. Our results indicate that within the family of HLA-DRw52-associated haplotypes DR beta chain genes may have been transferred from one haplotype to another. The implications of these findings 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

  • Bach, F.: The HLA class 11 genes and products: the HLA-D region. Immunol. Today 6: 89–94, 1985

    Google Scholar 

  • Bodmer, J. and Bodmer, W.: Histocompatibility 1984. Immunol. Today 5: 251–254, 1984

    Google Scholar 

  • Böhme, J., Andersson, M., Andersson, G., Möller, E., Peterson, P. A., and Rask, L.: HLA-DRβ genes vary in number between different DR specificities whereas the number of DQβ genes is constant. J. Immunol. 135: 2149–2155, 1985

    Google Scholar 

  • Bontrop, R. E., Schreuder,G. M. T., Elferink, D. G.,Mikulski, M. M. A., Geerse, R., and Giphart, M. J.: Molecular, serologic and functional evidence for an apparent HLA-DR triplet. J. Immunol. 137: 211–216, 1986a

    Google Scholar 

  • Bontrop, R., Ottenhoff, T., van Miltenburg, R., Elferink, D., de Vries, R., and Giphart, M.: Quantitative and qualitative differences in HLA-DR molecules correlated with antigen presentation capacity. Eur. J. Immunol. 16: 133–138, 1986b

    Google Scholar 

  • Bontrop, R. E., Tilanus, M., Mikulski, M., van Eggermond, M., Termijtelen, A., and Giphart, M. J.: Polymorphisms within the HLA-DR3 haplotypes. I. HLA-DR polymorphisms detected at the protein and DNA levels are reflected by T cell recognition. Immunogenetics 23: 401–405, 1986c

    Google Scholar 

  • Bosch, M. L., Termijtelen, A., Gerrets, R., Schreuder, G. M. T., Bontrop, R. E., and Giphart, M. J.: Polymorphisms within the HLA-DRw6 haplotypes. II. Protein charge heterogeneity reflects MLC subtyping of HLA-DRw6 homozygous cells. Immunogenetics 22: 23–33, 1985

    Google Scholar 

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

    Google Scholar 

  • Kaufman, J. F., Auffray, C., Korman, A. J., Shackelford, D. A., and Strominger, J. L.: The class II molecules of the human and murine histocompatibility complex. Cell 36: 1–13, 1984

    Google Scholar 

  • Larhammar, D., Servenius, B., Rask, L., and Peterson, P. A.: Characterization of an HLA-DR beta pseudogene. Proc. Natl. Acad. Sci. U.S.A. 82: 1475–1479, 1985

    Google Scholar 

  • Long, E. O., Wake, C. T., Strubin, M., Gross, N., Acolla, R. S., Carrel, S., and Mach, B.: Isolation of distinct cDNA clones encoding HLA-DR beta chains by use of an expression assay. Proc. Natl. Acad. Sci. U.S.A. 79: 7465–7469, 1982

    Google Scholar 

  • Nadler, L. M., Stashenko, P., Hardy, R., Pesando, J. M., Yunis, E. J., and Schlossman, S. F.: Monoclonal antibodies defining serologically distinct HLA-D/DR related la-like antigens in man (1981). Hum. Immunol. 1: 77–90, 1981

    Google Scholar 

  • Ollier, W., Doxiadis, I., Jaraquemada, D., Okoye, R., Grosse-Wilde, H., and Festenstein, H.: First level testing of HLA-D “blank” HTC. In E. D. Albert, M. P. Baur, and W. R. Mayr: Histocompatibility Testing 1984, pp. 281–285, Springer-Verlag, Berlin, 1984

    Google Scholar 

  • Ottenhoff, T. H. M., Elferink, D. G., Termijtelen, A., Koning, F., and de Vries R. R. P. HLA-class II repertoire of atigen specific T cells. I. The main restriction determinants are associated with HLAD/DR and not with DP and DQ. Hum. Immunol. 13: 117–123, 1985

    Google Scholar 

  • Paulsen, G., Qvigstad, E., Gaudernack, G., Rask, L., Winchester, R., and Thorsby, E.: Identification, at the genomic level, of an HLADR restriction element for cloned antigen-specific T cells. J. Exp. Med. 161: 1569–1574, 1985

    Google Scholar 

  • Rollini, P., Mach, B., and Gorski, J.: Linkage map of three HLA-DR beta-chain genes: evidence for a recent duplication event. Proc. Natl. Acad. Sci. U.S.A. 82: 7197–7201, 1985

    Google Scholar 

  • Rosenshine, S., Cascino, I., Zeevi, A., Duquesnoy, R. J., and Trucco, M.: DQ α and β RFLP reveals the composition of the DQ molecule recognized by T cell clones. Immunogenetics 23: 187–196, 1986

    Google Scholar 

  • Spies, T., Sorrentino, R., Boss, J. M., Okada, K., and Strominger, J.: Structural organization of the DR subregion of the human major histocompatibility complex. Proc. Natl. Acad. Sci. U.S.A. 82: 5165–5169, 1985

    Google Scholar 

  • Termijtelen, A., van Leeuwen, A., and Rood, J. J.: HLA-linked lymphocyte activating determinants. Immunol. Rev. 66: 79–101, 1982

    Google Scholar 

  • Termijtelen, A., Tilanus, M. G. J., Engelen, I., Koning, F., and van Rood, J. J.: Molecular localization of LB-Q1, a DRw52-like T cell recognition epitope and identification at the genomic level of associated shared hybridizing fragments. Hum. Immunol., in press, 1987

  • Tilanus, M. G. J., Morrolli, B., van Eggermond, M. C. J. A., Schreuder, G. M. T., de Vries, R. R. P., and Giphart, M. J.: Dissection of HLA class II haplotypes in HLA-DR4 homozygous individuals. Immunogenetics 23: 333–340, 1986

    Google Scholar 

  • Weyand, C. M., Goronzy, J., and Fathman, C. G.: Human T-cell clones used to define functional epitopes on HLA-class II molecules. Proc. Natl. Acad. Sci. U.S.A. 83: 762–766, 1986

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bontrop, R.E., Tilanus, M.G.J., Mikulski, M.M.A. et al. Polymorphism and complexity of HLA-DR: evidence for intra-HLA-DR region crossing-over events. Immunogenetics 27, 40–45 (1988). https://doi.org/10.1007/BF00404442

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00404442

Keywords

Navigation