title: Human heart-infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins.
abstract: BACKGROUND
  beta-Hemolytic streptococcal infection in developing countries still causes thousands of causes of rheumatic heart disease, demanding surgical valve correction. Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal-M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte-dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions.
  
  
  RESULTS
  We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients. We tested their capacity to recognize streptococcal M protein-derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions. Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level. Five of these clones are CD4+, and one is CD8+.
  
  
  CONCLUSIONS
  The presence of heart-M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease. The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.
authors.affiliation: Instituto do Coração, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Guilherme
authors.forename: E
authors.initials: E
authors.lastname: Cunha-Neto
authors.forename: V
authors.initials: V
authors.lastname: Coelho
authors.forename: R
authors.initials: R
authors.lastname: Snitcowsky
authors.forename: P M
authors.initials: PM
authors.lastname: Pomerantzeff
authors.forename: R V
authors.initials: RV
authors.lastname: Assis
authors.forename: F
authors.initials: F
authors.lastname: Pedra
authors.forename: J
authors.initials: J
authors.lastname: Neumann
authors.forename: A
authors.initials: A
authors.lastname: Goldberg
authors.forename: M E
authors.initials: ME
authors.lastname: Patarroyo
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins; D002465:Cell Movement; D002999:Clone Cells; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011506:Proteins / Q000276:immunology; D012214:Rheumatic Heart Disease / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D010455:Peptides; D011506:Proteins; C014689:streptococcal M protein