Streptococcal M protein extracted by nonionic detergent. III. Correlation between immunological cross-reactions and structural similarities with implications for antiphagocytosis.

Abstract

Three immunologically cross-reactive and non-cross-reactive streptococcal M proteins were analyzed by a chromatographic tryptic peptide mapping system. The results indicate that cross-reactions correlate with the extent of structural similarity among the M protein molecules analyzed. The data also reveal that free lysine is released by the action of trypsin from these three M proteins, suggesting a common lys-lys or arg-lys sequence. In addition, only one peptide has been found to be common within all three M types. This limited structural relatedness among the three M proteins examined indicates that sequence variation plays a major role in the immunological specificity of the M antigens. However, despite sequence variation, all M protein molecules have a common antiphagocytic activity. The fact that no common opsonic antibody has yet been found, even against limited M types, argues against this biological activity being solely the result of a common sequence. Based on these data, it is suggested that the antiphagocytic effect of M protein may be due to a conformationally created environment on the surface of the molecule which is selected by both immunological and biological pressure.

Heterogeneity of type-specific and cross-reactive antigenic determinants within a single M protein of group A streptococci.

“…By radiocompetitive assays he obtained evidence that suggested that opsonic antisera bound to the majority of the antigenic sites on the M6 molecule, whereas nonopsonic, cross-reactive antisera raised against heterologous serotypes of M protein reacted with only a small percentage of the antigenic sites recognized by M6 antiserum. Furthermore, the cross-reactions among M types were correlated with the presence of common peptide fragments, which suggested a certain degree of structural similarity among cross-reactive serotypes of M protein (15). The question as to whether or not certain of the cross-reactive determinants are buried or inaccessible in the intact M protein molecule, however, was not addressed.…”

“…Preincubation with the smaller peptides, CB3-7, resulted in . The opsonic inhibitory activity of each of the pep M proteins was assayed by mixing 0.1 ml of diluted serum with 100/~g pep M protein dissolved in 0.1 ml PBS, incubating the mixture at 37°C for 30 min, and using the treated serum to preopsonize type-24 or type-6 streptococci as previously described (15).…”

Streptococcal M protein: molecular design and biological behavior

“…Recognizing this limitation, other procedures for extracting M protein from whole streptococci or their isolated cell walls were attempted. These included sonic oscillation (25,157), alkali (47,84), group C bacteriophage-associated lysin (43,79), nonionic detergent (64,65), nitrous acid (91), cyanogen bromide (202), and guanidine hydrochloride extraction (178), all of which were usually coupled to a particular purification scheme. However, in nearly all cases the final purified M protein exhibited extensive heterogeneity.…”

Presence of two distinct regions in the coiled-coil structure of the streptococcal Pep M5 protein: relationship to mammalian coiled-coil proteins and implications to its biological properties.

“…Several serologically distinct variants of the M protein have been recognized over the years, and the immunity conferred by the induced antibodies to a given M type is essentially type specific (1,2,5).…”