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 × 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 subdominant 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.