Restriction in the Usage of Variable β Regions in T-cells Infiltrating Valvular Tissue from Rheumatic Heart Disease Patients

Figueroa, Fernando; González, Marisol I.; Carrión, Flavio; Lobos, Christian A.; Turner, F.M.; Lasagna, N.; Valdés, F

doi:10.1006/jaut.2002.0620

Cited by 16 publications

(6 citation statements)

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“…The high frequency and the persistence of T-cell oligoclonal expansions in the damaged heart valves seem to be associated with the progression of the disease [41], probably due to the T-cell recognition of several heart tissue proteins exposed by local lesions. In agreement with these data, it has been described that it is possible to detect T-cell expansions in damaged heart valves even 20 years after the acute RF episode [42]. …”

Section: T-cell Repertoiresupporting

confidence: 72%

Rheumatic Fever: From Sore Throat to Autoimmune Heart Lesions

Guilherme

Kalil

2004

Int Arch Allergy Immunol

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Molecular mimicry between streptococci and heart components has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). In this review, we present data from cellular autoimmune responses, focusing on the interactions between HLA class II molecules, streptococcal peptides and heart tissue proteins and T-cell receptor (TCR) usage. HLA-DR7DR53 associated with DQ molecules seem to be related with the development of valvular lesions in severe RHD patients. DR7DR53 molecules were also involved in the recognition of an immunodominant M5 peptide in these patients. T cells infiltrating RHD hearts displayed several oligoclonal expansions. Intralesional T-cell clones presenting identical TCR-BVBJ AVAJ and -CDR3 sequences were able to recognize several antigens with little or low homology, showing an intramolecular degenerate pattern of antigen recognition. Peripheral blood mononuclear cells of rheumatic fever (RF) patients produced proinflammatory cytokines, and intralesional mononuclear cells from severe RHD patients produced predominantly Th1-type cytokines. These results illustrate the complex mechanisms leading to heart tissue damage in RF/RHD patients.

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Section: T-cell Repertoiresupporting

confidence: 72%

Rheumatic Fever: From Sore Throat to Autoimmune Heart Lesions

Guilherme

Kalil

2004

Int Arch Allergy Immunol

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“…After activation of valvular endothelium, mimicking T cells migrate into the avascular valve through the endocardium and are stimulated by local valve Ags. In the valve, the T cells secrete IFN-␥, leading to Th1-mediated granuloma formation in the form of Aschoff nodules, whereas T cells continue to infiltrate the valve through neovascularized regions even years after acute disease (70).…”

Section: Discussionmentioning

confidence: 99%

T Cell Mimicry and Epitope Specificity of Cross-Reactive T Cell Clones from Rheumatic Heart Disease

Ellis

Hildebrand

et al. 2005

The Journal of Immunology

120

109

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Mimicry between streptococcal M protein and cardiac myosin is important in the pathogenesis of rheumatic heart disease. M protein-specific human T cell clones derived from rheumatic carditis were cross-reactive with human cardiac myosin, and laminin, a valve protein. Among the 11 CD4+ and CD8+ cross-reactive T cell clones, at least 6 different reactivity patterns were distinguished, suggesting different degrees of cross-reactivity and a very diverse T cell repertoire. The latter was confirmed by a heterogeneous Vβ gene and CDR3 usage. HLA restriction and Th1 cytokine production in response to rM6 protein were preserved when the T cell clones were stimulated by human cardiac myosin or other α-helical proteins, such as tropomyosin and laminin. The cross-reactive human T cell clones proliferated to B2 and B3A, dominant peptide epitopes in the B repeat region of streptococcal M protein. In human cardiac myosin, epitopes were demonstrated in the S2 and light meromyosin regions. In our study, T cell mimicry was defined as recognition of structurally related Ags involved in disease and recognized by the same T cell. Mimicry in our study was related to α-helical coiled coil proteins which have a repetitive seven-aa residue periodicity that maintains α-helical structure and thus creates a high number of degenerate possibilities for recognition by T cells. The study of human T cell clones from rheumatic heart disease revealed potential sites of T cell mimicry between streptococcal M protein and human cardiac myosin and represents some of the most well-defined T cell mimicry in human autoimmune disease.

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“…In agreement with these findings, Figueroa et al [21] showed the presence of expanded TCR-BV families in the valve tissue of RHD patients several years after the initial streptococcal infection. In both works, the specificity of clonal expansions was not evaluated.…”

Section: Discussionmentioning

confidence: 66%