title: T cell recognition of Neisseria meningitidis class 1 outer membrane proteins. Identification of T cell epitopes with selected synthetic peptides and determination of HLA restriction elements.
abstract: No vaccine is yet available against serogroup B meningococci, which are a common cause of bacterial meningitis. Some outer membrane proteins (OMP), LPS, and capsular polysaccharides have been identified as protective Ag. The amino acid sequence of the protective B cell epitopes present within the class 1 OMP has been described recently. Synthetic peptides containing OMP B cell epitopes as well as capsular polysaccharides or LPS protective B cell epitopes have to be presented to the immune system in association with T cell epitopes to achieve an optimal Ir. The use of homologous, i.e., meningococcal, T cell epitopes has many advantages. We therefore investigated recognition sites for human T cells within the meningococcal class 1 OMP. We have synthesized 16 class 1 OMP-derived peptides encompassing predicted T cell epitopes. Peptides corresponding to both surface loops and trans-membrane regions (some of which occur as amphipathic beta-sheets) of the class 1 OMP were found to be recognized by T cells. In addition, 10 of 11 peptides containing predicted amphipathic alpha-helices and four of five peptides containing T cell epitope motifs according to Rothbard and Taylor (Rothbard, J. B., and W. R. Taylor. 1988. EMBO J 7:93) were recognized by lymphocytes from one or more volunteers. Some of the T and B cell epitopes were shown to map to identical regions of the protein. At least six of the peptides that were found to contain T cell epitopes show homology to constant regions of the meningococcal class 3 OMP and the gonococcal porins PIA and PIB. Peptide-specific T cell lines and T cell clones were established to investigate peptide recognition in more detail. The use of a panel of HLA-typed APC revealed clear HLA-DR restriction patterns. It seems possible now to develop a (semi-) synthetic meningococcal vaccine with a limited number of constant T cell epitopes that cover all HLA-DR locus products.
authors.affiliation: National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Wiertz
authors.forename: J A
authors.initials: JA
authors.lastname: van Gaans-van den Brink
authors.forename: G M
authors.initials: GM
authors.lastname: Schreuder
authors.forename: A A
authors.initials: AA
authors.lastname: Termijtelen
authors.forename: P
authors.initials: P
authors.lastname: Hoogerhout
authors.forename: J T
authors.initials: JT
authors.lastname: Poolman
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D002999:Clone Cells; D000939:Epitopes; D006684:HLA-DR Antigens / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D006684:HLA-DR Antigens; D010455:Peptides