Molecular evidence for antigen-driven immune responses in cardiac lesions of rheumatic heart disease patients

Rheumatic heart disease (RHD) is a sequel of post-streptococcal throat infe ction. Molecular mimicry between streptococcal and heart components has bee n proposed as the triggering factor of the disease, and CD4(+) T cells have been found predominantly at pathological sites in the heart of RHD patient s. These infiltrating T cells are able to recognize streptococcal M protein peptides, involving mainly 1-25, 81-103 and 163-177 N-terminal amino acids residues. In the present work we focused on the TCR beta chain family (TCR BV) usage and the degree of clonality assessed by beta chain complementari ty-determining region (CDR)-3 length analysis. We have shown that in chroni c RHD patients, TCR BV usage in peripheral blood mononuclear cells (PBMC) p aired with heart-infiltrating T cell lines (HIL) is not suggestive of a sup erantigen effect. Oligoclonal T cell expansions were more frequently observ ed in HIL than in PBMC, Some major BV expansions were shared between the mi tral valve (Miv) and left atrium (LA)T cell lines, but an in-depth analysis of BJ segments usage in these shared expansions as well as nucleotide sequ encing of the CDR3 regions suggested that different antigenic peptides coul d be predominantly recognized in the Miv and the myocardium, Since differen t antigenic proteins probably are constitutively represented in myocardium and valvular tissue, these findings could suggest a differential epitope re cognition at the two lesional heart sites after a common initial bacterial challenge.