STRUCTURAL COMPARISON AND EPITOPE ANALYSIS OF OUTER-MEMBRANE PROTEIN PIA FROM STRAINS OF NEISSERIA-GONORRHOEAE WITH DIFFERING SEROVAR SPECIFICITIES

The sequences of the por genes, encoding outer-membrane protein PI, ha ve been obtained from a number of strains of Neisseria gonorrhoeae tha t express PIA molecules with differing serovar specificities. The infe rred amino acid sequences of the mature proteins each comprise 308 res idues and show considerable homology, with the degree of sequence vari ation between PIA molecules being considerably less than seen previous ly with PIB, but more evenly distributed throughout the molecule. The positions of sequence variation are largely confined to the regions pr edicted to form one of eight surface-exposed loops, suggesting a more widespread distribution of potential antigenic diversity. The deduced amino acid sequences were used to synthesize peptides for epitope mapp ing experiments. Some epitopes responsible for serovar specificity or recognized by bactericidal monoclonal antibodies could be identified o n the basis of their reactivity with simple linear peptides, whilst ot hers recognized conformational epitopes. By comparison of sequence dif ferences with mAb reactivity it was possible to identify regions that appear to contribute to such determinants, including separated regions of the molecule which together were required for the formation of the conformational epitopes. All the epitopes identified lie at or close to the apices of the predicted surface-exposed loops 1, 3, 6 or 8, foc using attention on these regions as accessible targets for immune atta ck.