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 infection. Molecular mimicry between streptococcal and heart components has been proposed as the triggering factor of the disease, and CD4(+) T cells have been found predominantly at pathological sites in the heart of RHD patients. 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 complementarity-determining region (CDR)-3 length analysis. We have shown that in chronic RHD patients, TCR BV usage in peripheral blood mononuclear cells (PBMC) paired with heart-infiltrating T cell lines (HIL) is not suggestive of a superantigen effect. Oligoclonal T cell expansions were more frequently observed in HIL than in PBMC. Some major BV expansions were shared between the mitral 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 sequencing of the CDR3 regions suggested that different antigenic peptides could be predominantly recognized in the Miv and the myocardium. Since different antigenic proteins probably are constitutively represented in myocardium and valvular tissue, these findings could suggest a differential epitope recognition at the two lesional heart sites after a common initial bacterial challenge.
Guilherme
L
L
Heart Institute-InCor, University of São Paulo, School of Medicine, São Paulo, Brazil.
Dulphy
N
N
Douay
C
C
Coelho
V
V
Cunha-Neto
E
E
Oshiro
S E
SE
Assis
R V
RV
Tanaka
A C
AC
Pomerantzeff
P M
PM
Charron
D
D
Toubert
A
A
Kalil
J
J
D000293:Adolescent; D000942:Antigens, Bacterial; D015551:Autoimmunity; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology; D012214:Rheumatic Heart Disease / Q000276:immunology* / Q000473:pathology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C014689:streptococcal M protein