NMR-STUDIES ON THE STRUCTURE FUNCTION CORRELATIONS OF T-CELL-EPITOPE ANALOGS FROM PERTUSSIS TOXIN/

A synthetic tridecapeptide, corresponding to the 30-42 fragment of the S1 subunit of pertussis toxin, has been structurally characterised by using NMR spectroscopy. The molecule corresponds to a T-cell epitope of the bacterial toxin which has been extensively analysed with the al anine scanning approach to check the relevance of each residue for the biological activity of the peptide. Five of these Ala-substituted ana logs have also been spectroscopically studied. In the experimental con ditions used, different extents of helicity were found for the six pep tides in a way which cannot be related to their capabilities of of bin ding to major histocompatibility complex (MHC) class II and inducing T -cell proliferation. Backbone flexibility around helical transient con formations seems to constitute the structural intermediate step betwee n the structure of the corresponding sequence within the parental prot ein and in the MHC class II complex. A model of the latter complex, wh ich accounts for the different biological activities of the analogs, i s proposed.