HUMAN HEART-INFILTRATING T-CELL CLONES FROM RHEUMATIC HEART-DISEASE PATIENTS RECOGNIZE BOTH STREPTOCOCCAL AND CARDIAC PROTEINS

Background beta-Hemolytic streptococcal infection in developing countr ies still causes thousands of cases of rheumatic heart disease, demand ing surgical valve correction. Antigenic mimicry between self and stre ptococcal components has been proposed as the triggering factor leadin g to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal-M protein cross-reactive antibodies have been dem onstrated, heart tissue damage seems to be T lymphocyte-dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions. Methods and Results We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart d isease patients. We tested their capacity to recognize streptococcal M protein-derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein seq uences tested, only synthetic peptides corresponding to regions 1 thro ugh 25, 81 through 103, and 163 through 177 were simultaneously recogn ized with heart protein fractions. Interestingly, regions 81 through 1 03 and 163 through 177 have been known to bear heart cross-reactive ep itopes at the antibody level. Five of these clones are CD4(+), and one is CD8(+). Conclusions The presence of heart-M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involv ement in the pathogenesis of this disease. The dissection of protectiv e and pathogenic epitopes of streptococcal M protein is an important s tep in allowing the development of a safe anti-streptococcal synthetic vaccine.