T-cell reactivity against streptococcal antigens in the periphery mirrors reactivity of heart-infiltrating T lymphocytes in rheumatic heart disease patients

T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic hear t disease (RHD). We searched for immunodominant T-cell M5 epitopes among RH D patients with defined clinical outcomes and compared the T-cell reactivit ies of peripheral blood and intralesional T cells from patients with severe RHD. The role of HLA class II molecules in the presentation of M5 peptides was also evaluated. We studied the T-cell reactivity against M5 peptides a nd heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesi onal and peripheral T-cell clones from RHD patients. Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequentl y recognized by PBMC from RHD patients than by those from controls. The M5 peptide encompassing residues 81 to 96 [M5(81-96) peptide] was most frequen tly recognized by PBMC from HLA-DR7(+) DR53(+) patients with severe RHD, an d 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81-103) reg ion. Heart proteins were recognized more frequently by PBMC from patients w ith severe RHD than by those from patients with mild RHD. The similar patte rn of T-cell reactivity found with both peripheral blood and heart-infiltra ting T cells is consistent with the migration of M-protein-sensitized T cel ls to the heart tissue. Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensit ized T cells from the heart lesion.