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Tolerance and immunity to the inducible self antigen C-reactive protein in transgenic mice.

Klein, TC; Döffinger, R; Pepys, MB; Rüther, U; Kyewski, B; (1995) Tolerance and immunity to the inducible self antigen C-reactive protein in transgenic mice. Eur J Immunol , 25 (12) pp. 3489-3495. 10.1002/eji.1830251242.

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Abstract

The understanding of immunological tolerance has been greatly aided by the development of transgenic animal models in which expression of a specific T cell receptor (or B cell receptor) and its cognate self antigen is experimentally controlled. In most cases, expression of the self antigen was constitutive and did not allow for variation of its time- and dose-dependent expression pattern, parameters which are known to influence the balance of tolerance versus immunity. We describe a transgenic model in which expression of human C-reactive protein (hCRP), an acute-phase protein, is tightly controlled at basal levels (female mice express around 10(-9) M and male mice 5 x 10(-7) M circulating hCRP) and is highly inducible (induction factor of 25-500). T cells from C57BL/6 mice recognize two epitopes of hCRP termed A (residues 79-95) and B (residues 87-102). Different efficacies of presentation in vitro and in vivo identify epitope A as sub-dominant and epitope B as dominant. T cells of non-induced hCRP transgenic mice are tolerant to the dominant epitope, but reactive to the subdominant epitope. A hCRP-specific IgG antibody response is detectable in transgenic mice, but is weaker than in littermates. Upon induction of hCRP, both T cell epitopes are presented by thymic and splenic antigen-presenting cells (APC) in vivo. Kinetics of presentation by splenic APC closely match serum kinetics of hCRP, whereas presentation in the thymus is considerably prolonged. This model enables epitope-specific T cell tolerance to be studied as a function of time- and dose-dependent expression of the self antigen.

Type: Article
Title: Tolerance and immunity to the inducible self antigen C-reactive protein in transgenic mice.
Location: Germany
DOI: 10.1002/eji.1830251242
Keywords: Amino Acid Sequence, Animals, Antigen Presentation, B-Lymphocytes, C-Reactive Protein, Epitopes, Female, Humans, Immune Tolerance, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, T-Lymphocytes
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/1551972
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