Role of macrophage-dependent determinant selection in induction phase of streptococcal carditis.

A genetically controlled antigen-presentation function in macrophages is proposed to explain the induction phase of streptococcal carditis. Antigenic determinants in strains of beta-haemolytic streptococci causing rheumatic fever are selected by macrophages, through the operation of immune response (Ir) genes, to be presented to T lymphocytes. Cross-reactivity between the selected determinants and heart tissue components generates clones of autoreactive T cells. Autoimmunity will develop if, coincidental with the presentation of the relevant antigenic determinant, regulation of T-cell production is disturbed. This hypothesis explains the capacity of different strains of streptococcus to produce rheumatic fever and also the variability in host susceptibility to the disease.