Activation of human class-II restricted T cell clones by short peptides

CD4+ T cells typically recognize 11-15 amino acid long peptides bound to major histocompatiblity compex (MHC) class II molecules. Using soluble peptide combinatorial libraries in the positional scanning format (PS-SPCL) we have previously defined the spectrum of ligands for a human autoreactive myelm basic protein peptide 87-99 (MBP(87-99))-specific T cell clone (TCC) and identified high potency ligands that stimulate the TCC at picomolar concentrations. To define the minimal peptide length required to activate the TCC we tested a panel of truncated variants of the high potency ligand. Using this approach, we demonstrate that 5 amino acid long peptides can activate the TCC as efficiently as the autoantigen used to establish the TCC. Moreover, non-overlapping N- and C- terminal fragments of the same optimal ligand both activate the TCC. The same peptide fragments were used to establish new CD4+ T cell lines that recognized the peptide in the context of MHC class II The results demonstrate that CD4+ T cells are highly flexible not only in their recognition of peptide structure but also in their peptide length requirements.