TERMINATION OF PERIPHERAL TOLERANCE TO A T-CELL EPITOPE BY HETEROCLITIC ANTIGEN ANALOGS

Treating mice with an immunodominant T cell epitope from moth cytochro me c (MCC88-103) can induce T cell unresponsiveness under certain cond itions of administration. In this report, we determined whether T cell tolerance to MCC88-103 in adult animals can be overcome by immunizati on with cross-reactive analogues of the tolerizing Ag, A panel of anal ogues of the tolerogen were tested for their capacity to terminate the tolerant state following in vivo immunization. As analyzed by their s timulatory capacity for a representative MCC88-103-specific T cell clo ne, this panel covered a wide range of cross-reactivity, including non antigenic, antagonistic, weakly, and strongly antigenic peptides, Inte restingly, only heteroclitic analogues, as measured in vitro by their enhanced antigenicity for the T cell clone that was specific for MCC88 -103, were capable of breaking tolerance. Thus, an immune response to the cross-reactive, heteroclitic analogues of tolerized self Ags may r epresent a mechanism by which Ag molecular mimicry operates.