ANTIGENIC DOMAINS OF STREPTOCOCCAL Pep

M protein of the group A streptococcus is an elongated, alpha-helical coiledcoil molecule that extends from the bacterial cell surface as a flexible fibrillar structure (1, 2). It is a major virulence factor for the bacteria, by virtue of its property of impeding the phagocytosis of the organisms (3). >75 serologically distinct variants of the M protein have been recognized over the years and, in the human, the immunity conferred by the induced antibodies to a given M type is essentially type specific (3-7). However, immunological crossreactions occur among some of the M protein serotypes (3-7). The crossreaction between types 5 and 6 M proteins is one such example (6, 8, 9). The crossreactivity of the type 5 M protein with the type 6 M protein is retained in its peptic fragment Pep M5 (8), which represents nearly the amino-terminal half of the native M5 molecule (10). With the exception of the nonhelical N-terminal 12-residue segment, the Pep M5 protein exhibits structural characteristics of alpha-helical coiled-coil proteins (11, 12). Based on the distribution of the nonpolar and charged amino acid residues, as well as internal homology, there are two structurally distinct regions (domains) within the coiled-coil structure of the Pep M5 molecule. The Nterminal domain of the Pep M5 protein carries a significantly higher net negative charge than its carboxy-terminal domain, and has been implicated in the antiphagocytic function of the molecule (1 1). In the present study, peptides derived from the two structurally distinct domains of the Pep M5 protein have been used (a) to determine whether both domains contain antigenic epitopes and (b) to identify the domains of the Pep M5 protein containing the epitope(s) crossreactive with the M6 protein.