Cross-sensitization to haptens: formation of common haptenic metabolites, T cell recognition of cryptic peptides, and true T cell cross-reactivity.
To analyze T cell cross-reactivity to para-compounds, we established CD4(+) T cell hybridomas from mice immunized with adducts of self-globin and one of three different para-compounds: p-aminophenol, p-phenylenediamine, or Bandrowski's base. Some of the hybridomas obtained reacted not only to the immunizing antigen, but also to metabolically related para-compounds, bound to the same protein, thus suggesting formation of common metabolites. Other hybridomas cross-reacted to globin adducts of metabolically unrelated para-compounds, which denotes them as truly cross-reactive cells whose TCR failed to distinguish among the different haptens. One of these hybridomas also reacted against a non-haptenated, cryptic peptide of hemoglobin but not to the full-length native protein. As this hybridoma reacted even more strongly to the respective peptide after it was haptenated, recognition of the native, cryptic peptide was apparently due to true cross-reactivity. To conclude, true T cell cross-reactivity to haptens does occur, as well as the formation of a common reactive metabolite, and T cell recognition of cryptic self-peptides may underlie cross-sensitization to chemicals.
Wulferink
Marty
M
Institute for Research on Environmental Medicine at Heinrich Heine University, Düsseldorf, Germany.
Dierkes
Sabine
S
Gleichmann
Ernst
E
D000595:Amino Acid Sequence; D000627:Aminophenols / Q000276:immunology; D000818:Animals; D001324:Autoantigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D005914:Globins / Q000737:chemistry / Q000276:immunology; D006241:Haptens / Q000276:immunology* / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology*; D010655:Phenylenediamines / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000627:Aminophenols; D001324:Autoantigens; D006241:Haptens; D009842:Oligopeptides; D010655:Phenylenediamines; C051597:Bandrowski's base; D005914:Globins; C026729:4-aminophenol; C029728:4-phenylenediamine