T Cell Response in Rheumatic Fever: Crossreactivity Between Streptococcal M Protein Peptides and Heart Tissue Proteins

Luiza      Guilherme; Kellen   C.   Fae; Sandra   E.   Oshiro; Ana   C.   Tanaka; Pablo   M.   A. Pomerantzeff; Jorge      Kalil

doi:10.2174/138920307779941488

Abstract

Molecular mimicry between streptococcal and human proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). In this review we focus on the studies on genetic susceptibility markers involved in the development of RF/RHD and molecular mimicry mediated by T cell responses of RHD patients against streptococcal antigens and human tissue proteins. We identified several M protein epitopes recognized by peripheral T cells of RF/RHD patients and by heart tissue infiltrating T cell clones of severe RHD patients. The regions of the M protein preferentially recognized by human T cells were also recognized by murine T cells. By analyzing the T cell receptor (TCR) we observed that some Vβ families detected on the periphery were oligoclonal expanded in the heart lesions. These results allowed us to confirm the major role of T cells in the development of RHD lesions.

Keywords: Rheumatic fever, rheumatic heart disease, Streptococcus pyogenes, T cell response, autoimmunity, molecular mimicry, M protein, heart proteins