Skip to main content

Advertisement

Log in

Allelic variations clustered in the antigen binding sites of HLA-Bw62 molecules

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

Abstract

HLA-Bw62 is a serologically defined class I antigen specificity, but we show that it represents a family of five distinct alleles in this study. Five variants of HLA-Bw62 antigens were identified by isoelectric focusing, and sequencing studies revealed that these are a family of closely related alleles differing from one another by one to six amino acid substitutions at eight positions: 63 in the α1 domain and 94, 95, 97, 99, 113, 152, and 156 in the α2 domain. These substitutions are located in the two α-helices and two adjacent β-strands, and the side chains of most amino acids face into the antigen binding groove. Functional assays using an in vitro generated Epstein-Barr virus (EBV)-specific Bw62-restricted cytotoxic T lymphocyte clone indicated that the minimal structural variations located in the antigen binding sites of the HLA-Bw62 variant molecules could affect the presentation of the nominal EBV antigen. This study revealed that the HLA-Bw62 antigen family consists of at least five closely related alleles, and further demonstrated that these alleles with minimal structural variations might play distinct functional roles in regard to antigen presentation.

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

  • Albert, E. D., Chandanayingyong, D., Thomson, J. S., Zhao, T., Hammon, M. G., Naito, S., and Sierp, G. M.: Antigen society #9 report (Bw46 and the subgroups of B15). In B. Dupont (ed.): Immunobiology of HLA, vol 1, pp. 153–156, Springer-Verlag, New York, NY, 1989

    Google Scholar 

  • Biddison, W. E., Krangel, M. S., Strominger, J. L., Ward, F. E., Shearer, G. M., and Shaw, S.: Virus-immune cytotoxic T cells recognize structural differences between serologically indistinguishable HLA-A2 molecules. Hum Immunol 3: 225–232, 1980

    Google Scholar 

  • Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C.: Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329: 506–512, 1987a

    Google Scholar 

  • Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C.: The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329: 512–518, 1987b

    Google Scholar 

  • Bjorkman, P. J. and Parham, P.: Structure, function and diversity of class I major histocompatibility molecules. Annu Rev Biochem 59: 253–288, 1990

    Google Scholar 

  • Bodmer, J. G., Marsh, S. G. E., Albert, E. D., Bodmer, W. F., Dupont, B., Erlich, H. A., Mach, B., Mayr, W. R., Parham, P., Sasazuki, T., Schreuder, G. M. Th., Strominger, J. L., Svejgaard, A., and Terasaki, P. I.: Nomenclature for factors of the HLA system, 1990. Hum Immunol 31: 186–194, 1991

    Google Scholar 

  • Bodmer, J. G., Marsh, S. G. E., Albert, E. D., Bodmer, W. F., Dupont, B., Erlich, H. A., Mach, B., Mayr, W. R., Parham, P., Sasazuki, T., Schreuder, G. M. Th., Strominger, J. L., Svejgaard, A., and Terasaki, P. I.: Nomenclature for factors of the HLA system, 1991. Tissue Antigens 39: 161–173, 1992

    Google Scholar 

  • Burrows, S. R., Sculley, T. B., Misko, I. S., Schmidt, C., and Moss, D. J.: An Epstein-Barr virus-specific cytotoxic T cell epitope in EBV nuclear antigen 3 (EBNA 3). J Exp Med 171: 345–349, 1990a

    Google Scholar 

  • Burrows, S. R., Misko, I. S., Sculley, T. B., Schmidt, C., and Moss, D. J.: An Epstein-Barr virus-specific cytotoxic T-cell epitope present on A- and B-type transformants. J Virol 64: 3974–3976, 1990b

    Google Scholar 

  • Castano, A. R. and Lopez de Castro, J. A.: Structure of the HLA-A*0204 antigen, found in South American Indians. Spatial clustering of HLA-A2 subtype polymorphism. Immunogenetics 34: 281–285, 1991

    Google Scholar 

  • Choo, S. Y., Fan, L.-A., and Hansen, J. A.: A novel HLA-B27 allele maps B27 allospecificity to the region around position 70 in the α1 domain. J Immunol 147: 174–180, 1991

    Google Scholar 

  • Choo, S. Y., Abramov, V., and Hansen, J. A.: Molecular heterogeneity in the HLA-Bw62 antigen. In K. Tsuji (ed.): HLA 1991, Oxford University Press, Oxford, in press, 1992

    Google Scholar 

  • Clark, B. D., Park, M. S., Tonai, R., and Terasaki, P. I.: Serologic and biochemical analysis of HLA B15 and B5 complexes. Hum Immunol 20: 47–57, 1987

    Google Scholar 

  • Cowan, E. P., Jordan, B. R., and Coligan, J. E.: Molecular cloning and DNA sequence analysis of genes encoding cytotoxic T lymphocyte-defined HLA-A3 subtypes: the E1 subtype. J Immunol 135: 2835–2841, 1985

    Google Scholar 

  • Falk, K., Rötzchke, O., and Rammensee, H.-G.: Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature 348: 248–251, 1990

    Google Scholar 

  • Falk, K., Rötzschke, O., Stevanovic, S., Jung, G., and Rammensee, H.-G.: Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351: 290–296, 1991

    Article  CAS  PubMed  Google Scholar 

  • Fan, L.-A., Choo, S. Y., Beatty, P. G., and Hansen, J. A.: HLA-Bw62 variants identified by a cytotoxic T-lymphocyte clone and isoelectric focusing gel electrophoresis. In B. Dupont (ed.): Immunobiology of HLA, vol 2, pp. 117–119, Springer-Verlag, New York, NY, 1989

    Google Scholar 

  • Fleischhauer, K., Kernan, N. A., O'Reilly, R. J., Dupont, B., and Yang, S. Y.: Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44. N Engl J Med 323: 1818–1822, 1990

    Google Scholar 

  • Garrett, T. P. J., Saper, M. A., Bjorkman, P. J., Strominger, J. L., and Wiley, D. C.: Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature 342: 692–696, 1989

    Google Scholar 

  • Gaston, J. S. H., Rickinson, A. B., and Epstein, M. A.: Epstein-Barr virus-specific cytotoxic T lymphocytes as probes of HLA polymorphism. Heterogeneity of T cell-restricting determinants associated with the serologically defined HLA-A2 antigen. J Exp Med 158: 280–293, 1983

    Google Scholar 

  • Gotch, F., Rothbard, J., Howland, K., Townsend, A., and McMichael, A.: Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2. Nature 326: 881–882, 1987

    Google Scholar 

  • Hansen, J. A., Martin, P. J., and Nowinski, P. R.: Monoclonal antibodies identifying a novel T-cell antigen and Ia antigens of human lymphocytes. Immunogenetics 10: 247–260, 1980

    Google Scholar 

  • Heath, W. R., Kane, K. P., Mescher, M. F., and Sherman, L. A.: Alloreactive T cells discriminate among a diverse set of endogenous peptides. Proc Natl Acad Sci USA 88: 5101–5105, 1991

    Google Scholar 

  • Hogan, K. T., Clayberger, C., Le, A.-X. T., Walk, S. F., Ridge, J. P., Parham, P., Krensky, A. M., and Engelhard, V. H.: Cytotoxic T lymphocyte-defined epitope differences between HLA-A2.1 and HLA-A2.2 map to two distinct regions of the molecule. J Immunol 141: 4005–4011, 1988

    Google Scholar 

  • Hunt, H. D., Munitz, T. I., and Pease, L. R.: Alloreactive cytotoxic T lymphocytes recognize epitopes determined by both the α helices and β sheets of the class I peptide binding site. J Exp Med 175: 821–829, 1992

    Google Scholar 

  • Jardetzky, T. S., Lane, W. S., Robinson, R. A., Madden, D. R., and Wiley, D. C.: Identification of self peptides bound to purified HLA-B27. Nature 353: 326–329, 1991

    Google Scholar 

  • Little, A.-M. and Parham, P.: The HLA-Bw75 subtype of B15: molecular characterization and comparison with crossreacting antigens. Tissue Antigens 38: 186–190, 1991

    Google Scholar 

  • Lopez de Castro, J. A.: HLA-B27 and HLA-A2 subtypes: structure, evolution and function. Immunol Today 10: 239–246, 1989

    Google Scholar 

  • Madden, D. R., Gorga, J. C., Strominger, J. L., and Wiley, D. C.: The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 353: 321–325, 1991

    Google Scholar 

  • Mattson, D. H., Handy, D. E., Bradley, D. A., Coligan, J. E., Cowan, E. P., and Biddison, W. E.: DNA sequences of the genes that encode the CTL-defined HLA-A2 variants M7 and DK1. Immunogenetics 26: 190–192, 1987

    Google Scholar 

  • Moots, R. J., Matsui, M., Pazmany, L., McMichael, A. J., and Frelinger, J. A.: A cluster of mutations in HLA-A2 α2 helix abolishes peptide recognition by T cells. Immunogenetics 34: 141–148, 1991

    Google Scholar 

  • Murray, R. J., Wang, D., Young, L. S., Wang, F., Rowe, M., Kieff, E., and Rickinson, A. B.: Epstein-Barr virus-specific cytotoxic T-cell recognition of transfectants expressing the virus-coded latent membrane protein LMP. J Virol 62: 3747–3755, 1988

    Google Scholar 

  • Murray, R. J., Kurilla, M. G., Griffin, H. M., Brooks, J. M., Mackett, M., Arrand, J. R., Rowe, M., Burrows, S. R., Moss, D. J., Kieff, E., and Rickinson, A. B.: Human cytotoxic T-cell responses against Epstein-Barr virus nuclear antigens demonstrated by using recombinant vaccinia viruses. Proc Natl Acad Sci USA 87: 2906–2910, 1990

    Google Scholar 

  • Pamer, E. G., Harty, J. T., and Bevan, M. J.: Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature 353: 852–855, 1991

    Google Scholar 

  • Parham, P., Barnstable, C. J., and Bodmer, W. F.: Use of a monoclonal antibody (W6/32) in structural studies of HLA-A, B, C antigens. J Immunol 123: 342–349, 1979

    Google Scholar 

  • Pohla, H., Kuon, W., Tabaczewski, P., Doerner, C., and Weiss, E. H.: Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles. Immunogenetics 29: 297–307, 1989

    Google Scholar 

  • Romero, P., Corradin, G., Leuscher, I. F., and Maryanski, J. L.: H-2Kd-restricted antigenic peptides share a simple binding motif. J Exp Med 174: 603–612, 1991

    Google Scholar 

  • Rötzschke, O., Falk, K., Deres, K., Schild, H., Norda, M., Metzger, J., Jung, G., and Rammensee, H.-G.: Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 348: 252–254, 1990

    Google Scholar 

  • Saper, M. A., Bjorkman, P. J., and Wiley, D. C.: Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol 219: 277–318, 1991

    CAS  PubMed  Google Scholar 

  • Taketani, S., Krangel, M. S., Spits, H., de Vries, J., and Strominger, J. L.: Structural analysis of an HLA-B7 antigen variant detected by cytotoxic T lymphocytes. J Immunol 133: 816–821, 1984

    Google Scholar 

  • Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D., and McMichael, A. J.: The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959–968, 1986

    Google Scholar 

  • Van Bleek, G. M. and Nathenson, S. G.: Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kd molecule. Nature 348: 213–216, 1990

    Google Scholar 

  • Wallace, L. E., Rowe, M., Gaston, J. S. H., Rickinson, A. B., and Epstein, M. A.: Cytotoxic T cell recognition of Epstein-Barr virus-infected B cells. III. Establishment of HLA-restricted cytotoxic T cell lines using IL-2. Eur J Immunol 12: 1012–1018, 1982

    Google Scholar 

  • Yang, S. Y.: Population analysis of class I HLA antigens by one-dimensional isoelectric focusing gel electrophoresis: workshop summary report. In B. Dupont (ed.): Immunobiology of HLA, vol 1, pp. 309–331, Springer-Verlag, New York, NY, 1989a

    Google Scholar 

  • Yang, S. Y.: A standardized method for detection of HLA-A and HLA-B alleles by 1D-IEF. In B. Dupont (ed.): Immunobiology of HLA, vol 1, pp. 332–335, Springer-Verlag, New York, NY, 1989b

    Google Scholar 

  • Zemmour, J., and Parham, P.: HLA class I nucleotide sequences, 1991. Hum Immunol 31: 195–205, 1991

    Google Scholar 

  • Zinkernagel, R. M. and Doherty, P. C.: MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T cell restriction specificity, function and responsiveness. Adv Immunol 27: 51–177, 1979

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M83191–83195.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoon Choo, S., Fan, La. & Hansen, J.A. Allelic variations clustered in the antigen binding sites of HLA-Bw62 molecules. Immunogenetics 37, 108–113 (1993). https://doi.org/10.1007/BF00216833

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00216833

Keywords

Navigation