T helper cell epitope of rabies virus nucleoprotein defined by tri- and tetrapeptides.
T cell clones and subsequently hybridomas were generated from rabies virus-immune C3H/He mice to an immunodominant epitope of the viral nucleoprotein, termed 31D, that had previously been identified by a 15-amino acid-long synthetic peptide. T cells to this epitope that by phenotypical and functional characteristics belonged to the T helper cell subset were shown to respond to most rabies and rabies-related viruses. In order to define the minimal sequence needed to elicit a response from 31D-specific T cell clones or hybridomas, a number of peptides of varied lengths, i.e. 3-32 amino acids long, were tested. The ability of the peptides to induce a response was inversely correlated in their lengths, i.e., short peptides (3-5 amino acids long) had to be used at 10(6) times higher concentrations as compared to long peptides (15 or 32 amino acids long). Conversely, the specificity of the T cell response was directly correlated to the length of the peptides, i.e., while the response to 15-amino acid-long peptides exhibited a high degree of specificity, the response to 3- to 5-amino acid-long peptides showed a high degree of flexibility. The long as well as the short peptides had to be presented in association with I-Ek. We speculate that in this system the T cell receptor interacts predominantly with a peptide-induced modification of the I-Ek molecule.
Ertl
H C
HC
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Dietzschold
B
B
Otvos
L
L
D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology; D006825:Hybridomas; D008222:Lymphokines / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology*; D010456:Peptides, Cyclic / Q000276:immunology; D011820:Rabies virus / Q000276:immunology*; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; D008222:Lymphokines; D009698:Nucleoproteins; D009842:Oligopeptides; D010456:Peptides, Cyclic