T-cell mimicry of streptococcal M protein and cardiac myosin epitopes by T-cell clones from rheumatic heart disease

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 crossreactive with human cardiac myosin, and laminin, a valve protein. Among the 11 CD4+ and CD8+ crossreactive T-cell clones, at least six different reactivity patterns were distinguished, suggesting different degrees of crossreactivity and a very diverse T-cell repertoire. The latter was confirmed by a heterogeneous Vβ-gene and CDR3 usage. The HLA-restriction and Th1 cytokine production in response to rM6 protein was preserved when the T-cell clones were stimulated by human cardiac myosin or other α-helical proteins, such as tropomyosin and laminin. The crossreactive 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 (LMM) regions. 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.