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.