How an autoimmune reaction triggered by molecular mimicry between streptococcal M protein and cardiac tissue proteins leads to heart lesions in rheumatic heart disease.

Abstract	Molecular mimicry between microbial antigens and host tissue is suggested as a mechanism for post-infectious autoimmune disease. In the present work we describe the autoimmune reactions of two severe rheumatic heart disease (RHD) patients, through an analysis of heart-infiltrating T-cell repertoire, antigen recognition, and cytokine production induced by specific antigens. T-cell clones derived from oligoclonally expanded T cells in the heart cross-recognized M5 peptides, heart tissue-derived proteins, and myosin peptides. We show, using binding affinity assays, that an immunodominant streptococcal peptide (M5(81-96)) is capable of binding to the HLA-DR53 molecule. The same peptide was recognized by an infiltrating T-cell clone from a patient carrying HLA-DR15, DR7, and DR53 molecules. This suggests that this peptide is probably presented to T cells in the context of the HLA-DR53 molecule. Cross-reactive heart-infiltrating T cells activated by the M5 protein and its peptides and by heart tissue-derived proteins produced predominantly inflammatory cytokines. Interleukin (IL)-4 was produced in small amounts by mitral valve intralesional T-cell lines and clones. Altogether, these results suggest that mimicry between streptococcal antigens and heart-tissue proteins, combined with high inflammatory cytokine and low IL-4 production, leads to the development of autoimmune reactions and cardiac tissue damage in RHD patients.
Authors	K C Faé, S E Oshiro, A Toubert, D Charron, J Kalil, L Guilherme
Journal	Journal of autoimmunity (J Autoimmun) Vol. 24 Issue 2 Pg. 101-9 (Mar 2005) ISSN: 0896-8411 [Print] England
PMID	15829402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens Antigens, Bacterial Bacterial Outer Membrane Proteins Carrier Proteins Cytokines streptococcal M protein
Topics	Antigens (immunology) Antigens, Bacterial (immunology) Autoimmunity (immunology) Bacterial Outer Membrane Proteins (immunology) Carrier Proteins (immunology) Cells, Cultured Child Cytokines (immunology) Humans Male Molecular Mimicry (immunology) Rheumatic Heart Disease (immunology, pathology) T-Lymphocytes (immunology)

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