Minimum length of an idiotypic peptide and a model for its binding to a major histocompatibility complex class II molecule

Abstract

We have defined the minimum length of a synthetic peptide which can activate I-E(d)-restricted BALB/c T cell clones specific for a mutated self-antigen: an idiotope on the syngeneic λ2315 immunoglobulin light chain. A peptide comprising residues 91-101 of the λ2315 sequence had full stimulatory potency. Surprisingly, a peptide analogue in which His97 was deleted was almost fully active. Truncated, deleted or substituted peptide analogues did not distinguish between seven T cell clones that use different α/β T cell receptors. The 91-101 region in the λ2315 light chain does not form an amphipathic helix even though such a helix has been suggested to be important for T cell epitopes. Further, a motif proposed by Rothbard and Taylor as being common to T cell immunogenic peptides is not necessary for the λ2315 idiotypic peptide. Comparison with seven other I-E(d)-restricted peptides revealed that the peptides are generally positively charged and have two basic amino acids clustered around the centre. On the basis of a model of the class II molecule peptide binding site, we suggest that these positively charged residues may interact with the negatively charged residues at positions 114(Glu) and 155(Asp) of the E(β)(d) chain.