Delayed Hypersensitivity to Purified Streptococcal M Protein in Guinea Pigs and in Man

Abstract

Purified M antigen extracted from Group A streptococci was not homogeneous but was distributed among several molecular populations of protein. The type-specificity of delayed hypersensitivity to a selected single population of M protein, which appeared immunochemically pure, was studied. The majority of normal human adults showed delayed skin hypersensitivity to the highly purified fractions of both rare and common M serotypes with equal frequency. Similar delayed skin reactions were elicited often in normal adult guinea pigs. Like human infants, baby guinea pigs were more tolerant to purified M protein, and in these young animals type-specific delayed allergy could be demonstrated soon after immunization with a single dose of purified M protein in Freund's complete adjuvant. Weak cross-reactions between M serotypes were observed in some animals suggesting contaminating antigens of unknown nature. Both type-specific and cross-reactive delayed hypersensitivity were confirmed by in vitro inhibition of migration of peritoneal macrophages of sensitized guinea pigs. Although some degree of type-specificity of delayed allergy was induced in young guinea pigs, the ubiquitous nature of cross-reacting determinants was apparent. the latter may constitute contaminating antigens or may be common antigenic determinants of the M moiety uncovered during purification. The possibilities that the guinea pig model of human delayed allergy to M protein may prove useful in evaluating the purity of M protein vaccines and in studying the role of type-specific delayed hypersensitivity in immunity to streptococcal infections were discussed.