title: Role of single amino acids in the recognition of a T cell epitope.
abstract: T cell epitopes can be defined by the use of synthetic peptides, which when added to APC efficiently mimic naturally processed Ag. Free peptide is thought to bind to cell-surface MHC glycoproteins and the TCR then recognizes the resulting complex. The specificity of a tetanus toxin-specific human Th cell clone was investigated using a complete replacement set of peptides in which every amino acid within the minimal T cell epitope was replaced by each of the 19 alternative genetically coded amino acids. Within the minimal epitope, found to be YSYFPSVI (tetanus toxin 593-600), a small number of substitutions could be made without significant loss of activity, defined as substitutions giving peptides whose activity fell within +/- 3 SD of the mean parent response. Y593 could be substituted with F, W, M, L, V, and I; S594 with G and T; Y595, F596, and P597 with no other amino acids; S598 with A; V599 with S, and I600 with L. Rank ordering of the substitutions allowed a precise description to be made of MHC and/or TCR interaction with each amino acid side chain within the epitope. Simplified theoretic calculations based on this study indicate that class II T cell recognition has a specificity greater than 1 in 10(8). Competition experiments indicate that Y595, F596, P597, and I600 are critical for binding of this epitope to its restricting element, HLA DR4Dw14.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Suhrbier
authors.forename: S J
authors.initials: SJ
authors.lastname: Rodda
authors.forename: P C
authors.initials: PC
authors.lastname: Ho
authors.forename: P
authors.initials: P
authors.lastname: Csurhes
authors.forename: H
authors.initials: H
authors.lastname: Dunckley
authors.forename: A
authors.initials: A
authors.lastname: Saul
authors.forename: H M
authors.initials: HM
authors.lastname: Geysen
authors.forename: C M
authors.initials: CM
authors.lastname: Rzepczyk
mesh_terms: D000595:Amino Acid Sequence; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell