Heart infiltrating T cell clones from a rheumatic heart disease patient display a common TCR usage and a degenerate antigen recognition pattern.
CD4+ T cells are most likely the ultimate effectors of chronic heart lesions in rheumatic heart disease (RHD). We have demonstrated that infiltrating CD4+ T cell clones were able to recognize several heart tissue and streptococcal antigens by molecular mimicry. Clonality analysis of the mitral valve and myocardium infiltrating T cell lines showed several oligoclonal expansions, some of which were found in both sites of the lesions. The results presented in this study showed a degenerate pattern of reactivity of intralesional T cell clones from one RHD patient. Four mitral valve and one papillar muscle-derived T cell clones, presenting the same TCR-BV13 BJ2S7 with same sequences of the CDR3 region recognized different antigens. They expressed two alpha chains at the RNA level and the AV AJ segments were the same for mitral valve T cell clones, but not for the papillar muscle-derived T cell clone. Two other intralesional T cell clones using the same TCR-BV3 JB2S1 segments with identical CDR3 sequences also recognized different antigens. These results indicate that intralesional T cell clones with common TCR usage can recognize several epitopes that probably amplify the deleterious immune reaction. These data, allow us to hypothesize that degenerate T cell recognition may lead to intramolecular degenerate reactivity against epitopes with low homology. This can be a novel mechanism of epitope spreading, of relevance in the increase of epitopes targets that can activate cross-reactive autoimmune T cells.
Faé
K
K
Heart Institute (nCor), School of Medicine, University of São Paulo, Brazil.
Kalil
J
J
Toubert
A
A
Guilherme
L
L
D000941:Antigens / Q000276:immunology*; D000942:Antigens, Bacterial; D001324:Autoantigens / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D002648:Child; D006801:Humans; D008297:Male; D008943:Mitral Valve / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012214:Rheumatic Heart Disease / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D000942:Antigens, Bacterial; D001324:Autoantigens; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D011948:Receptors, Antigen, T-Cell; C014689:streptococcal M protein