Expansion of CD4 T cells expressing a highly restricted TCR structure specific for a single parasite epitope correlates with high pathology in murine schistosomiasis.
The hepatic immunopathology in schistosomiasis mansoni is mediated by CD4 T cells specific for egg antigens and varies considerably among mouse strains. Previous studies in high pathology C3H mice suggested that a strong T cell response was due to the recognition of an immunodominant epitope within the major egg antigen Sm-p40 (Sm-p40(234-246)). Using a panel of T cell hybridomas, we have now examined the egg antigen-specific TCR repertoire in two high pathology strains, C3H and CBA. We found that nearly half of the hybridomas responded to the Sm-p40(234-246 )epitope and, of these, nearly all expressed Valpha11.3 associated with Vbeta8. Furthermore, in response to egg antigen stimulation, transcript levels of Valpha11.3J36 (the most prevalent rearrangement expressed by Sm-p40(234-246)-specific hybridomas), increased in high pathology (CBA) but not in low pathology BALB/c strains. Our findings suggest that exacerbated schistosome egg-induced immunopathology can be driven by T cells expressing a highly restricted TCR structure specific for a single parasite epitope.
Finger
Eduardo
E
Immunology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
Brodeur
Peter H
PH
Hernandez
Hector J
HJ
Stadecker
Miguel J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology*; D003001:Cloning, Molecular; D005260:Female; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018510:RNA, Helminth / Q000737:chemistry / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology*; D012550:Schistosoma mansoni / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology; D017422:Sequence Analysis, DNA
D000947:Antigens, Helminth; D015801:Helminth Proteins; D016056:Immunodominant Epitopes; D018510:RNA, Helminth; D016693:Receptors, Antigen, T-Cell, alpha-beta; C055560:p40 egg antigen, Schistosoma