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.