Skip to main content
SpringerLink
Log in

Three new class I HLA alleles: structure of mRNAs and alternative mechanisms of processing

  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Sixteen HLA class I clones have been isolated from a SV40-transformed human fibroblast line (GM637) cDNA library. The clones, characterized by hybridization to ABC locus-specific probes and sequence analysis, correspond to transcripts from four different class I genes: A2, A10, Cw4, and Cw6 (or Cw7), as implied by cell typing. Only the A2 sequence was known. The nucleotide and deduced amino acid sequence of the new alleles are reported here, and their structural features are discussed. Two independent cDNAs of A2 specificity display an unusual polyadenylation site located 100 by upstream from the canonical one. Moreover, two cDNAs pertaining to the same C allele display two alternative mechanisms of splicing, which cause either presence or absence in mature transcripts of the transmembrane exon 5 sequence. Transcripts missing this region are predicted to synthesize a nonmembrane-bound, secreted antigen. A soluble protein, specifically reacting with class I-specific HLA antibodies, is found in the supernatant of the GM637 cells. The significance of HLA class I transcripts generated by differential processing is discussed.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Archibald, A. L., Thompson, N. A., and Kvist, S.: A single nucleotide difference at the 3′ end of an intron causes differential splicing of two histocompatibility genes. EMBO J 5: 957–965, 1986

    Google Scholar 

  • Birnstiel, M. L., Busslinger, M., and Strub, K.: Transcription termination and 3′ processing: the end is in site! Cell 41: 349–359, 1985

    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 

  • Collins, T., Lapierre, L. A., Fiers, W., Strominger, J. L., and Pober, J. S.: Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A, B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci USA 83: 446–450, 1986

    Google Scholar 

  • Cowan, E. P., Jelachich, M. L., Biddison, W. E., and Coligan, J. E.: DNA sequence of HLA-All: remarkable homology with HLA-A3 allows identification of residues involved in epitopes recognized by antibodies and T cells. Immunogenetics 25: 241–250, 1987

    Google Scholar 

  • Duceman, B. W., Ness, D., Rende, R., Chorney, M. J., Srivastava, R., Greenspan, D. S., Pan, J., Weissman, S. M., and Grumet, F. C.: HLA-JY-328: mapping studies and expression of a polymorphic HLA class I gene. Immunogenetics 23: 90–99, 1986

    Google Scholar 

  • Early, P., Rogers, J., Davis, M., Calame, K., Bond, M., Wall, R., and Hood, L.: Two mRNAs can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways. Cell 20: 313–319, 1980

    Google Scholar 

  • Gething, M. J. and Sambrook, J.: Construction of influenza haemagglutinin genes that code for intracellular and secreted forms of the protein. Nature 300: 598–603, 1982

    Google Scholar 

  • Guild, B. C., Erikson, R. L., and Strominger, J. L.: HLA-A2 and HLAB7 antigens are phosphorylated in vitro by Rous sarcoma virus kinase (pp60v-src) at a tyrosine residue encoded in a highly con served exon of the intracellular domain. Proc Natl Acad Sci USA 80: 2894–2898, 1983

    Google Scholar 

  • Güssow, D., Rein, R. S., Meijer, I., de Hoog, W., Seemann, G. H. A., Hochstenbach, F. M., and Ploegh, H. L.: Isolation, expression, and the primary structure of HLA-Cwl and HLA-Cw2 genes: evolutionary aspects. Immunogenetics 25: 313–322, 1987

    Google Scholar 

  • Holmes, N. and Parham, P.: Exon shuffling in vivo can generate novel HLA class I molecules. EMBO J 4: 2849–2854, 1985

    Google Scholar 

  • Koller, B. H. and Orr, H. T.: Cloning and complete sequence of an HLA-A2 gene: analysis of two HLA-A alleles at the nucleotide level. J Immunol 134: 2727–2733, 1985

    Google Scholar 

  • Koller, B. H., Sidwell, B., De Mars, R., and Orr, H. T.: Isolation of HLA locus-specific DNA probes from the 3′-untranslated region. Proc Natl Acad Sci USA 81: 5175–5178, 1984

    Google Scholar 

  • Krangel, M. S.: Unusual RNA splicing generates a secreted form of HLA-A2 in a mutagenized B lymphoblastoid cell line. EMBO J 4: 1205–1210, 1985

    Google Scholar 

  • Krangel, M. S.: Secretion of HLA-A and -B antigens via an alternative RNA splicing pathway. J Exp Med 163: 1173–1190, 1986

    Google Scholar 

  • Kress, M., Cosman, D., Khoury, G., and Jay, G.: Secretion of a transplantation-related antigen. Cell 34: 189–196, 1983a

    Google Scholar 

  • Kress, M., Glaros, D., Khoury, G., and Jay, G.: Alternative RNA splicing in expression of the H-2K gene. Nature 306: 602–604, 1983b

    Google Scholar 

  • Lalanne, J. L., Transy, C., Guerin, S., Darche, S., Meulien, P., and Kourilsky, P.: Expression of class I genes in the major histocompatibility complex: identification of eight distinct mRNAs in DBA/2 mouse liver. Cell 41: 469–478, 1985

    Google Scholar 

  • Lehrman, M. A., Schneider, W. J., Sudhof, T. C., Brown, M. S., Goldstein, J. L., and Russel, D. W.: Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science 227: 140–146, 1985

    Google Scholar 

  • Lew, A. M., Maloy, W. L., and Coligan, J. E.: Characteristics of the expression of the murine soluble class I molecule (Q10). J Immunol 136: 254–258, 1986

    Google Scholar 

  • López de Castro, J. A., Strominger, J. L., Strong, D. M., and Orr, H. T.: Structure of crossreactive human histocompatibility antigens HLA-A28 and HLA-A2: possible implications for the generation of HLA polymorphism. Proc Natl Acad Sci USA 79: 3813–3817, 1982

    Google Scholar 

  • López de Castro, J. A., Bragado, R., Strong, D. M., and Strominger, J. L.: Primary structure of papain-solubilized human histocompatibility antigen HLA-1340 (-Bw60). An outline of alloantigenic determinants. Biochemistry 22: 3961–3969, 1983

    Google Scholar 

  • Malissen, M., Damotte, M., Birnbaum, D., Trucy, J., and Jordan, B. R.: HLA cosmid clones show complete, widely spaced human class I genes with occasional clusters. Gene 20: 485–489, 1982a

    Google Scholar 

  • Malissen, M., Malissen, B., and Jordan, B. R.: Exon/intron organization and complete nucleotide sequence of an HLA gene. Proc Natl Acad Sci USA 79: 893–897, 1982b

    Google Scholar 

  • Maniatis, T., Fritsch, E., and Sambrook, J.: Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, New York, 1982

    Google Scholar 

  • Mann, D. W., Stroynowsky, I., Hood, L., and Forman, J.: Cytotoxic T lymphocytes from mice with soluble class I Q10 molecules in their serum are not tolerant to membrane-bound Q10. J Immunol 138: 240–245, 1987

    Google Scholar 

  • Mayes, E. L. V. and Waterfield, M. D.: Biosynthesis of the epidermal growth factor receptor in A431 cells. EMBO J 3: 531–537, 1984

    Google Scholar 

  • N'Guyen, C., Sodoyer, R., Trucy, J., Strachan, T., and Jordan, B. R.: The HLA-AW24 gene: sequence, surroundings and comparison with the HLA-A2 and HLA-A3 genes. Immunogenetics 21: 479–489, 1985

    Google Scholar 

  • Nielsen, L. Staub, Jersild, C., Ryder, L. P., and Svejgaard, A.: HL-A antigen, gene and haplotype frequencies in Denmark. Tissue Antigens 6: 70–76, 1975a

    Google Scholar 

  • Nielsen, L. Staub, Ryder, L. P., and Svejgaard, A.: The third (AJ) segregant series. In: Histocompatibility Testing 1975, pp. 324–329, Munksgaard, Copenhagen, 1975b

    Google Scholar 

  • Okayama, H. and Berg, P.: A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol Cell Biol 3: 280–289, 1983

    Google Scholar 

  • Parham, R., Lomen, C. E., Lawlor, D. A., Ways, J. P., Holmes, N., Coppin, H. L., Salter, R. D., Wan, A. M., and Ennis, P. D.: Nature of polymorphism in HLA-A, -B, and -C molecules. Proc Natl Acad Sci USA 85: 4005–4009, 1988

    Google Scholar 

  • Pellegrino, M. A., Russo, C., and Allison, J. P.: HLA antigens in serum. Methods Enzymol 108: 614–625, 1984

    Google Scholar 

  • Ploegh, H. L., Orr, H. T., and Strominger, J. L.: Major histocompatibility antigens: the human (HLA-A, -B, -C) and routine (H-2K, H-2D) class I molecules. Cell 24: 287–299, 1981

    Google Scholar 

  • Rogers, M. J., Siwarski, D. F., Shacter, E., Maloy, W. L., Lillehoj, E. P., and Coligan, J. E.: Three distinct H-2Ks molecules differing at the carboxy terminus are expressed on a tumor from SJL/J mice. J Immunol 137: 3006–3012, 1986

    Google Scholar 

  • Rose, J. K. and Bergmann, J. E.: Expression from cloned cDNA of cellsurface secreted forms of the glycoprotein of vesicular stomatitis virus in eucaryofc cells. Cell 30: 753–762, 1982

    Google Scholar 

  • Rubin, L. A., Kurman, C. C., Fritz, M. E., Biddison, W. E., Bountin, B., Yarchoan, R., and Nelson, D. L.: Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 135: 3172–3177, 1985

    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

    Google Scholar 

  • Schreier, P. H. and Cortese, R.: A fast and simple method for sequencing DNA cloned in the single-stranded bacteriophage M13. J Mol Biol 129: 169–172, 1979

    Google Scholar 

  • Seemann, G. H. A., Rein, R. S., Brown, C. S., and Ploegh, H. L.: Gene conversion-like mechanisms may generate polymorphism in human class I genes. EMBO J 5: 547–552, 1986

    Google Scholar 

  • Setter, D. R., McGrogan, M., and Schimke, R. T.: Nucleotide sequence surrounding multiple polyadenylation sites in the mouse dihydrofolate reductase gene. J Biol Chem 257 5143–5147, 1982

    Google Scholar 

  • Shaw, G. and Kamen, R.: A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46: 659–667, 1986

    Google Scholar 

  • Sodoyer, R., Damotte, M., Delovitch, T. L., Trucy, J., Jordan, B. R., and Strachan, T.: Complete nucleotide sequence of a gene encoding a functional human class I histocompatibility antigen (HLA-Cw3). EMBO J 3: 879–885, 1984

    Google Scholar 

  • Sood, A. K., Pan, J., Biro, P. A., Pereira, D., Srivastava, R., Reddy, V. B., Duceman, B. W., and Weissman, S. M.: Structure and polymorphism of class I MHC antigen mRNA. Immunogenetics 22: 101–121, 1985

    Google Scholar 

  • Srivastava, R., Duceman, B. W., Biro, P. A.,Sood, A. K., and Weissman, S. M.: Molecular organization of the class I genes of human major histocompatibility complex. Immunol Rev 84: 93–121, 1985

    Google Scholar 

  • Stein, P., Barra, Y., Jay, G., and Strickland, S.: Expression of a secreted transplantation antigen gene during routine embryogenesis. Mol Cell Biol 6: 3397–3400, 1986

    Google Scholar 

  • Strachan, T., Sodoyer, R., Damotte, M., and Jordan, B. R.: Complete nucleotide sequence of a functional class I HLA gene, HLA-A3: implications for the evolution of HLA genes. EMBO J 3: 887–894, 1984

    Google Scholar 

  • Stroynowski, I., Soloski, M., Low, M. G., and Hood, L.: A single gene encodes soluble and membrane-bound forms of the major histocompatibility Qa-2 antigen: anchoring of the product by a phospholipid tail. Cell 50: 759–768, 1987

    Google Scholar 

  • Transy, C., Lalanne, J. L., and Kourilsky, P.: Alternative splicing in the 5′ moiety of the H-2K d gene transcript. EMBO J 3: 2383–2386, 1984

    Google Scholar 

  • Wan, A. M., Ennis, P., Parham, P., and Holmes, N.: The primary structure of HLA-A32 suggests a region involved in formation of the Bw4/Bw6 epitopes. J Immunol 137: 3671–3674, 1986

    Google Scholar 

  • Waneck, G. L., Sherman, D. H., Calvin, S., Allen, H., and Flavell, R. A.: Tissue-specific expression of cell-surface Qa-2 antigen from a transfected Q76 gene of C57BL/10 mice. J Exp Med 165: 1358–1370, 1987

    Google Scholar 

  • Wallach, D., Fellous, M., and Revel, M.: Preferential effect of γ interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature 299: 833–836, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. International Institute of Genetics and Biophysics, CNR, I-80125, Naples, Italy

    Luigi Scotto, Antonio Simeone & Edoardo Boncinelli

  2. Department of Hematology-Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299, I-00161, Rome, Italy

    Luciano Cianetti, Ugo Testa, Roberto La Valle, Giovanni Boccoli, Gianfranco Giannella & Cesare Peschle

Authors
  1. Luciano Cianetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ugo Testa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luigi Scotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberto La Valle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Simeone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giovanni Boccoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gianfranco Giannella
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cesare Peschle
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Edoardo Boncinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cianetti, L., Testa, U., Scotto, L. et al. Three new class I HLA alleles: structure of mRNAs and alternative mechanisms of processing. Immunogenetics 29, 80–91 (1989). https://doi.org/10.1007/BF00395855

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00395855

Keywords

Search

Navigation