title: Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99).
abstract: We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.
authors.affiliation: Neuroimmunology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vergelli
authors.forename: B
authors.initials: B
authors.lastname: Hemmer
authors.forename: U
authors.initials: U
authors.lastname: Utz
authors.forename: A
authors.initials: A
authors.lastname: Vogt
authors.forename: M
authors.initials: M
authors.lastname: Kalbus
authors.forename: L
authors.initials: L
authors.lastname: Tranquill
authors.forename: P
authors.initials: P
authors.lastname: Conlon
authors.forename: N
authors.initials: N
authors.lastname: Ling
authors.forename: L
authors.initials: L
authors.lastname: Steinman
authors.forename: H F
authors.initials: HF
authors.lastname: McFarland
authors.forename: R
authors.initials: R
authors.lastname: Martin
mesh_terms: D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D002999:Clone Cells; D015802:HLA-DR2 Antigen / Q000235:genetics; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects*; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D015802:HLA-DR2 Antigen; D008024:Ligands; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell