Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Feb 1;175(2):361–369. doi: 10.1084/jem.175.2.361

Genetic modulation of antigen presentation by HLA-B27 molecules

PMCID: PMC2119107  PMID: 1370680

Abstract

In studies of antigenic peptide presentation, we have found a healthy volunteer whose lymphoblastoid cells were unable to present three different virus-derived epitopes to cytotoxic T lymphocytes (CTL) despite expressing the correct restricting HLA-B27 molecules on the cell surface. B cell lines were established from other members of the donor's family, including individuals suffering from ankylosing spondylitis and related diseases, and were tested for their ability to function as target cells in the same assay. None of the eight B cell lines that expressed HLA-B27 presented a known peptide epitope to CTL. However, cells from a family member that expressed HLA-B8 could present an epitope peptide restricted by that molecule. The B27 molecule in this family proved to be the B2702 subtype on isoelectric focusing gels, appearing in exactly the same position as B2702 from other cell lines that did present the peptide. To exclude mutations resulting in noncharged amino acid substitutions, cDNA coding for B2702 was cloned from the proband's cell line and sequenced. No coding changes were found. The cloned cDNA was transfected into HLA-A- and B-negative HMy/C1R cells, and the B2702 molecules generated in this environment rendered these cells, after incubation with peptide, susceptible to lysis by peptide-specific CTL. These data are compatible with the presence of a factor(s), possibly HLA linked, interfering with antigen presentation by otherwise normal B2702 molecules in this family.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brewerton D. A., Hart F. D., Nicholls A., Caffrey M., James D. C., Sturrock R. D. Ankylosing spondylitis and HL-A 27. Lancet. 1973 Apr 28;1(7809):904–907. doi: 10.1016/s0140-6736(73)91360-3. [DOI] [PubMed] [Google Scholar]
  2. Cerundolo V., Elliott T., Elvin J., Bastin J., Rammensee H. G., Townsend A. The binding affinity and dissociation rates of peptides for class I major histocompatibility complex molecules. Eur J Immunol. 1991 Sep;21(9):2069–2075. doi: 10.1002/eji.1830210915. [DOI] [PubMed] [Google Scholar]
  3. Chen B. P., Rothbard J., Parham P. Apparent lack of MHC restriction in binding of class I HLA molecules to solid-phase peptides. J Exp Med. 1990 Sep 1;172(3):931–936. doi: 10.1084/jem.172.3.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Demotz S., Matricardi P. M., Irle C., Panina P., Lanzavecchia A., Corradin G. Processing of tetanus toxin by human antigen-presenting cells. Evidence for donor and epitope-specific processing pathways. J Immunol. 1989 Dec 15;143(12):3881–3886. [PubMed] [Google Scholar]
  6. Deverson E. V., Gow I. R., Coadwell W. J., Monaco J. J., Butcher G. W., Howard J. C. MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters. Nature. 1990 Dec 20;348(6303):738–741. doi: 10.1038/348738a0. [DOI] [PubMed] [Google Scholar]
  7. Ennis P. D., Zemmour J., Salter R. D., Parham P. Rapid cloning of HLA-A,B cDNA by using the polymerase chain reaction: frequency and nature of errors produced in amplification. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2833–2837. doi: 10.1073/pnas.87.7.2833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Falk K., Rötzschke O., Rammensee H. G. Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature. 1990 Nov 15;348(6298):248–251. doi: 10.1038/348248a0. [DOI] [PubMed] [Google Scholar]
  9. Frelinger J. A., Gotch F. M., Zweerink H., Wain E., McMichael A. J. Evidence of widespread binding of HLA class I molecules to peptides. J Exp Med. 1990 Sep 1;172(3):827–834. doi: 10.1084/jem.172.3.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gould K. G., Scotney H., Townsend A. R., Bastin J., Brownlee G. G. Mouse H-2k-restricted cytotoxic T cells recognize antigenic determinants in both the HA1 and HA2 subunits of the influenza A/PR/8/34 hemagglutinin. J Exp Med. 1987 Sep 1;166(3):693–701. doi: 10.1084/jem.166.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. He M., Wilde A., Kaderbhai M. A. A simple single-step procedure for small-scale preparation of Escherichia coli plasmids. Nucleic Acids Res. 1990 Mar 25;18(6):1660–1660. doi: 10.1093/nar/18.6.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hochberg M. C., Bias W. B., Arnett F. C., Jr Family studies in HLA-B27 associated arthritis. Medicine (Baltimore) 1978 Sep;57(5):463–475. doi: 10.1097/00005792-197809000-00005. [DOI] [PubMed] [Google Scholar]
  13. Hogan K. T., Shimojo N., Walk S. F., Engelhard V. H., Maloy W. L., Coligan J. E., Biddison W. E. Mutations in the alpha 2 helix of HLA-A2 affect presentation but do not inhibit binding of influenza virus matrix peptide. J Exp Med. 1988 Aug 1;168(2):725–736. doi: 10.1084/jem.168.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huet S., Nixon D. F., Rothbard J. B., Townsend A., Ellis S. A., McMichael A. J. Structural homologies between two HLA B27-restricted peptides suggest residues important for interaction with HLA B27. Int Immunol. 1990;2(4):311–316. doi: 10.1093/intimm/2.4.311. [DOI] [PubMed] [Google Scholar]
  15. Livingstone A. M., Powis S. J., Diamond A. G., Butcher G. W., Howard J. C. A trans-acting major histocompatibility complex-linked gene whose alleles determine gain and loss changes in the antigenic structure of a classical class I molecule. J Exp Med. 1989 Sep 1;170(3):777–795. doi: 10.1084/jem.170.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McMichael A. J., Gotch F. M., Rothbard J. HLA B37 determines an influenza A virus nucleoprotein epitope recognized by cytotoxic T lymphocytes. J Exp Med. 1986 Nov 1;164(5):1397–1406. doi: 10.1084/jem.164.5.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Monaco J. J., Cho S., Attaya M. Transport protein genes in the murine MHC: possible implications for antigen processing. Science. 1990 Dec 21;250(4988):1723–1726. doi: 10.1126/science.2270487. [DOI] [PubMed] [Google Scholar]
  18. Nathenson S. G., Geliebter J., Pfaffenbach G. M., Zeff R. A. Murine major histocompatibility complex class-I mutants: molecular analysis and structure-function implications. Annu Rev Immunol. 1986;4:471–502. doi: 10.1146/annurev.iy.04.040186.002351. [DOI] [PubMed] [Google Scholar]
  19. Neefjes J. J., Breur-Vriesendorp B. S., van Seventer G. A., Iványi P., Ploegh H. L. An improved biochemical method for the analysis of HLA-class I antigens. Definition of new HLA-class I subtypes. Hum Immunol. 1986 Jun;16(2):169–181. doi: 10.1016/0198-8859(86)90046-7. [DOI] [PubMed] [Google Scholar]
  20. Neefjes J. J., Doxiadis I., Stam N. J., Beckers C. J., Ploegh H. L. An analysis of class I antigens of man and other species by one-dimensional IEF and immunoblotting. Immunogenetics. 1986;23(3):164–171. doi: 10.1007/BF00373817. [DOI] [PubMed] [Google Scholar]
  21. Nixon D. F., Townsend A. R., Elvin J. G., Rizza C. R., Gallwey J., McMichael A. J. HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature. 1988 Dec 1;336(6198):484–487. doi: 10.1038/336484a0. [DOI] [PubMed] [Google Scholar]
  22. Powis S. J., Howard J. C., Butcher G. W. The major histocompatibility complex class II-linked cim locus controls the kinetics of intracellular transport of a classical class I molecule. J Exp Med. 1991 Apr 1;173(4):913–921. doi: 10.1084/jem.173.4.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rötzschke O., Falk K., Deres K., Schild H., Norda M., Metzger J., Jung G., Rammensee H. G. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature. 1990 Nov 15;348(6298):252–254. doi: 10.1038/348252a0. [DOI] [PubMed] [Google Scholar]
  24. Seemann G. H., Rein R. S., Brown C. S., Ploegh H. L. Gene conversion-like mechanisms may generate polymorphism in human class I genes. EMBO J. 1986 Mar;5(3):547–552. doi: 10.1002/j.1460-2075.1986.tb04245.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Spies T., Bresnahan M., Bahram S., Arnold D., Blanck G., Mellins E., Pious D., DeMars R. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature. 1990 Dec 20;348(6303):744–747. doi: 10.1038/348744a0. [DOI] [PubMed] [Google Scholar]
  26. Spies T., DeMars R. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature. 1991 May 23;351(6324):323–324. doi: 10.1038/351323a0. [DOI] [PubMed] [Google Scholar]
  27. Stam N. J., Vroom T. M., Peters P. J., Pastoors E. B., Ploegh H. L. HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. Int Immunol. 1990;2(2):113–125. doi: 10.1093/intimm/2.2.113. [DOI] [PubMed] [Google Scholar]
  28. Taylor P. M., Davey J., Howland K., Rothbard J. B., Askonas B. A. Class I MHC molecules rather than other mouse genes dictate influenza epitope recognition by cytotoxic T cells. Immunogenetics. 1987;26(4-5):267–272. doi: 10.1007/BF00346521. [DOI] [PubMed] [Google Scholar]
  29. Townsend A. R., Gotch F. M., Davey J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell. 1985 Sep;42(2):457–467. doi: 10.1016/0092-8674(85)90103-5. [DOI] [PubMed] [Google Scholar]
  30. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  31. Townsend A., Elliott T., Cerundolo V., Foster L., Barber B., Tse A. Assembly of MHC class I molecules analyzed in vitro. Cell. 1990 Jul 27;62(2):285–295. doi: 10.1016/0092-8674(90)90366-m. [DOI] [PubMed] [Google Scholar]
  32. Townsend A., Ohlén C., Bastin J., Ljunggren H. G., Foster L., Kärre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature. 1989 Aug 10;340(6233):443–448. doi: 10.1038/340443a0. [DOI] [PubMed] [Google Scholar]
  33. Townsend A., Ohlën C., Foster L., Bastin J., Ljunggren H. G., Kärre K. A mutant cell in which association of class I heavy and light chains is induced by viral peptides. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):299–308. doi: 10.1101/sqb.1989.054.01.038. [DOI] [PubMed] [Google Scholar]
  34. Trowsdale J., Hanson I., Mockridge I., Beck S., Townsend A., Kelly A. Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transporters. Nature. 1990 Dec 20;348(6303):741–744. doi: 10.1038/348741a0. [DOI] [PubMed] [Google Scholar]
  35. Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
  36. Wallace L. E., Rowe M., Gaston J. S., Rickinson A. B., Epstein M. A. Cytotoxic T cell recognition of Epstein-Barr virus-infected B cells. III. Establishment of HLA-restricted cytotoxic T cell lines using interleukin 2. Eur J Immunol. 1982 Dec;12(12):1012–1018. doi: 10.1002/eji.1830121206. [DOI] [PubMed] [Google Scholar]
  37. Wallny H. J., Rammensee H. G. Identification of classical minor histocompatibility antigen as cell-derived peptide. Nature. 1990 Jan 18;343(6255):275–278. doi: 10.1038/343275a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES