title: The immunodominant region of Staphylococcal nuclease is represented by multiple peptide sequences.
abstract: Several published reports have lead to the characterization of naturally processed peptides that are presented in association with either class I or class II MHC molecules. Most peptides isolated from class II molecules are heterogeneous in length and exhibit ragged amino and carboxy termini. An intriguing finding was that one region of a molecule was often represented by many distinct peptides, rather than by a single dominant peptide species. Each of the peptides representing this dominant region exhibited a common core of amino acids, suggesting that this core may play a significant role in the binding of the peptide to class II and the recognition by peptide-specific T cells. Work from our laboratory has focused on the mechanisms involved in the immunodominance of antigenic determinants using the bacterial antigen Staphylococcal nuclease (Nase) as a model. Using truncated synthetic peptides, we have identified the immunodominant determinant of Nase to be located within the region 81-100 with a minimal antigenic core of 91-100 as determined. Addition of five residues to the carboxy terminus of this peptide had a negative effect on T cell recognition of this region. The present studies were undertaken in an effort to determine the sequence of the naturally processed immunodominant Nase determinant(s) presented in association with I-Ek class II. Our results indicate that the dominant region of the Nase molecule is represented by at least four distinct peptide species that are predicted to lie between residues 86 and 106 with a common core sequence of 91-96. These results indicate that the negative effects of flanking regions are dependent upon length and amino acid composition, and thus the use of truncated peptides to study minimal antigenic determinants may be misleading.
authors.affiliation: Department of Immunology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Nikcevich
authors.forename: D
authors.initials: D
authors.lastname: Kopielski
authors.forename: A
authors.initials: A
authors.lastname: Finnegan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008836:Micrococcal Nuclease / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D010455:Peptides / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010455:Peptides; D008836:Micrococcal Nuclease