T-CELL CROSS-REACTIVITY TO HEAVY-METALS - IDENTICAL CRYPTIC PEPTIDES MAY BE PRESENTED FROM PROTEIN EXPOSED TO DIFFERENT METALS

The mechanisms by which metals induce activation of T cells and thus p roduce allergic and/or autoimmune reactions are still obscure, and the same is true for the mechanisms that underly T cell cross-reactivity to different heavy metal ions. In the present study, we investigated i nduction by metals of T cell reactions to cryptic peptides of bovine R Nase A. Murine CD4(+) T cell hybridomas specific for cryptic RNase pep tides presented from Au(III)-treated RNase were used as detection prob es. We showed that in vitro treatment of RNase with Pd(II), Pd(IV), Ni (IV), and partially Pt(IV), but not Au(I), Ni(II), or Pt(II), induced presentation of the same cryptic peptides as those presented from Au(I II)-treated RNase. That the former heavy metal ions, but not the latte r, were able to alter the antigenicity of RNase was reflected by their ability to induce conformational changes of RNase, as detected by cir cular dichroism spectroscopy. Furthermore, upon immunization against R Nase pretreated with these metals, CD4(+) T cell hybridomas specific f or unidentified cryptic peptides were obtained. In conclusion, ''metal -specific'' T cell reactions may be directed against cryptic peptides, and metal cross-reactivity in allergic individuals might be due to me tal-induced presentation of overlapping, but not identical, panels of cryptic peptides.