Self-reactive T cell hybridomas and tolerance. Same range of antigen dose dependence but higher numbers of self-reactive T cell hybridomas from mice in which self-tolerance has been broken by antiserum treatment.
Mechanisms of self-tolerance of 4-hydroxyphenylpyruvate dioxygenase (HPPD) are explored. It is well established that negative selection based on TCR affinity occurs in the thymus. We have investigated the frequency with which self-reactive T cell hybridomas can be obtained in relation to self-tolerance. Mice immunized with the self-form of HPPD gave rise to T cell hybridomas that were able to recognize self-protein and a synthetic peptide representing the T cell epitope, at higher Ag concentration than was necessary for recognition of allo-protein. The efficiency of negative selection was then reduced by treating neonatal mice with anti-HPPD antiserum. This reduced T cell tolerance of the self-protein, as judged by in vitro proliferation, and enabled self-reactive T cell hybridomas to be generated at a higher frequency. However, the Ag concentration requirements of these hybridomas for the self-protein and the self-peptide remained unaltered. The possibility that these findings reflect an auxiliary mechanism of self-tolerance based on frequencies of self-reactive T cells is discussed.
Schneider
S C
SC
German Rheumatology Research Center, Berlin.
Mitchison
N A
NA
D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018604:Epitope Mapping; D000939:Epitopes; D005260:Female; D006825:Hybridomas / Q000276:immunology*; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D000939:Epitopes; D010455:Peptides; D015111:4-Hydroxyphenylpyruvate Dioxygenase