AUTOANTIBODY PRODUCTION IN HEPATITIS-B E-ANTIGEN TRANSGENIC MICE ELICITED WITH A SELF T-CELL PEPTIDE AND INHIBITED WITH NONSELF PEPTIDES
AUTOANTIBODY PRODUCTION IN HEPATITIS-B E-ANTIGEN TRANSGENIC MICE ELICITED WITH A SELF T-CELL PEPTIDE AND INHIBITED WITH NONSELF PEPTIDES
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DOI：
10.1073/pnas.88.10.4348
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
JONES, JE
中科院分区：
文献类型：
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作者：
MILICH, DR;MCLACHLAN, A;JONES, JE
在表达B e抗原（HBeAg）的转基因小鼠中的研究表明，对同一转基因自身分子上的两个T细胞决定簇的自身耐受性可以显著不同。HBeAg上的主要T细胞位点是致耐受性的，而识别第二个T细胞位点的一部分T细胞逃避耐受诱导，持续存在于外周，并且可以通过单次注射12个残基的T细胞自身肽在体内激活。自身反应性T细胞介导体内自身抗体产生，足以中和血清中自身抗原的检测。此外，自身抗体的产生可以被与自身肽竞争结合主要组织相容性复合体分子的非自身肽抑制。该模型表明，对非隔离自身抗原上的免疫原性T细胞位点特异的T细胞可以逃避耐受诱导，更重要的是，可以介导体内自身反应性。此外，这些结果表明，合成的T细胞位点可能是有用的免疫制剂，以避免在持续性B病毒感染期间对HBeAg无应答。
Studies in hepatitis B e antigen (HBeAg)-expressing transgenic mice indicate that self tolerance to two T-cell determinants on the same transgenic self molecule can differ markedly. The dominant T-cell site on HBeAg is tolerogenic, whereas a proportion of T cells recognizing a second T-cell site evade tolerance induction, persist in the periphery, and can be activated in vivo by a single injection of a 12-residue T-cell self peptide. The self-reactive T cells mediate in vivo autoantibody production sufficient to neutralize detection of the autoantigen in serum. Furthermore, autoantibody production can be inhibited by nonself peptides that compete with the self peptide for binding to major histocompatibility complex molecules. This model illustrates that T cells specific for an immunogenic T-cell site on a nonsequestered autoantigen can escape tolerance induction and, more importantly, can mediate autoreactivity in vivo. Furthermore, these results suggest that synthetic T-cell sites may be useful as immunotherapeutic agents for the purpose of circumventing nonresponse to HBeAg during persistent hepatitis B virus infection.