Termination of peripheral tolerance to a T cell epitope by heteroclitic antigen analogues.
Treating mice with an immunodominant T cell epitope from moth cytochrome c (MCC(88-103)) can induce T cell unresponsiveness under certain conditions of administration. In this report, we determined whether T cell tolerance to MCC(88-103) in adult animals can be overcome by immunization with cross-reactive analogues of the tolerizing Ag. A panel of analogues of the tolerogen were tested for their capacity to terminate the tolerant state following in vivo immunization. As analyzed by their stimulatory capacity for a representative MCC(88-103)-specific T cell clone, this panel covered a wide range of cross-reactivity, including nonantigenic, antagonistic, weakly, and strongly antigenic peptides. Interestingly, only heteroclitic analogues, as measured in vitro by their enhanced antigenicity for the T cell clone that was specific for MCC(88-103), were capable of breaking tolerance. Thus, an immune response to the cross-reactive, heteroclitic analogues of tolerized self Ags may represent a mechanism by which Ag molecular mimicry operates.
Zügel
U
U
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Wang
R
R
Shih
G
G
Sette
A
A
Alexander
J
J
Grey
H M
HM
D000818:Animals; D010856:Columbidae; D003429:Cross Reactions; D003574:Cytochrome c Group / Q000008:administration & dosage / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry / Q000276:immunology; D009036:Moths; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*
D003574:Cytochrome c Group; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010446:Peptide Fragments