T cell mimicry and epitope specificity of cross-reactive T cell clones from rheumatic heart disease.

Abstract

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 Vbeta 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 alpha-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 alpha-helical coiled coil proteins which have a repetitive seven-aa residue periodicity that maintains alpha-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.

• Authors: Nadia M J Ellis, Ya Li, William Hildebrand, Vincent A Fischetti, Madeleine W Cunningham
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 8 Pg. 5448-56 (Oct 15 2005) ISSN: 0022-1767 [Print] United States
• PMID: 16210652 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Carrier Proteins
• Cytokines
• Epitopes, T-Lymphocyte
• HLA Antigens
• Receptors, Antigen, T-Cell
• streptococcal M protein
• Cardiac Myosins

Topics

• Amino Acid Sequence
• Antigens, Bacterial (immunology)
• Bacterial Outer Membrane Proteins (immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Cardiac Myosins (immunology)
• Carrier Proteins (immunology)
• Cell Communication (immunology)
• Cell Line
• Clone Cells
• Cytokines (metabolism)
• Epitopes, T-Lymphocyte (immunology)
• HLA Antigens (immunology)
• Humans
• Molecular Mimicry (immunology)
• Molecular Sequence Data
• Receptors, Antigen, T-Cell (immunology)
• Rheumatic Heart Disease (immunology)
• T-Lymphocytes (immunology)
• Th1 Cells (metabolism)