title: Activation of T cells by the ragged tail of MHC class II-presented peptides of the measles virus fusion protein.
abstract: The efficient and sustained immune response of an antigen requires T cell epitopes, capable of inducing a long lasting T cell memory. To detect T cell epitopes of the measles virus fusion protein (MV-F), the proliferation of lymphocytes from late convalescent donors in response to overlapping pentadecapeptides covering the whole protein sequence was studied. Three major immunodominant regions (F51-70, F121-135 and F211-225) containing promiscuous peptides induce proliferation in peripheral blood lymphocytes in approximately 50% of the donors. Potential DR1-restricted epitopes were mapped using an MHC competition binding assay. Both the proliferation and the binding data identified a DR1-restricted T cell epitope (F51-65). Contact sites of the peptide HQSLVIKLMPNITLL with MHC were characterized using substitution analogs. Alanine substitutions at most positions did not interfere with F51-65 binding. These analogs were therefore useful for studying the residues which were recognized by the TCR of MV- and F51-induced T cells lines. In addition to amino acid residues of the core of peptide F51-65 both the C-terminal and the N-terminal amino acids were essential for T cell interaction. Since peptides presented by class II molecules vary in length, these findings suggest that residues of the ragged tail are important for T cell activation. It is speculated that in late convalescent donors the length of the flanking sequence of MHC II-restricted peptides may play a role in controlling the heterogeneity of MV-specific T cell clones recruited as T helper/memory cells.
authors.affiliation: Laboratoire National de Santé, Luxembourg, Germany.
authors.forename: C P
authors.initials: CP
authors.lastname: Muller
authors.forename: W
authors.initials: W
authors.lastname: Ammerlaan
authors.forename: B
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: S
authors.initials: S
authors.lastname: Krauss
authors.forename: H
authors.initials: H
authors.lastname: Kalbacher
authors.forename: F
authors.initials: F
authors.lastname: Schneider
authors.forename: G
authors.initials: G
authors.lastname: Jung
authors.forename: K H
authors.initials: KH
authors.lastname: Wiesmüller
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001665:Binding Sites / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008459:Measles virus / Q000737:chemistry* / Q000276:immunology*; D010455:Peptides / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D014760:Viral Fusion Proteins