T cell response in rheumatic fever: crossreactivity between streptococcal M protein peptides and heart tissue proteins.
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 Vbeta 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.
Guilherme
Luiza
L
Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. luizagui@usp.br
Faé
Kellen C
KC
Oshiro
Sandra E
SE
Tanaka
Ana C
AC
Pomerantzeff
Pablo M A
PM
Kalil
Jorge
J
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D020022:Genetic Predisposition to Disease; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009206:Myocardium / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D012213:Rheumatic Fever / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001323:Autoantibodies; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C014689:streptococcal M protein