Genetic modulation of antigen presentation by HLA-B27 molecules

Laszlo Pazmany, Sarah Rowland-Jones, Stephane Huet, Ann Hill, Julian Sutton, Ruth Murray, Jill Brooks, Andrew McMichael

Research output: Contribution to journalArticle

55 Scopus citations

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 doned 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.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalJournal of Experimental Medicine
Volume175
Issue number2
DOIs
StatePublished - Feb 1 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Pazmany, L., Rowland-Jones, S., Huet, S., Hill, A., Sutton, J., Murray, R., Brooks, J., & McMichael, A. (1992). Genetic modulation of antigen presentation by HLA-B27 molecules. Journal of Experimental Medicine, 175(2), 361-369. https://doi.org/10.1084/jem.175.2.361