AUTOANTIBODY PRODUCTION IN HEPATITIS-B E-ANTIGEN TRANSGENIC MICE ELICITED WITH A SELF T-CELL PEPTIDE AND INHIBITED WITH NONSELF PEPTIDES

被引:73
作者
MILICH, DR
MCLACHLAN, A
RANEY, AK
HOUGHTEN, R
THORNTON, GB
MARUYAMA, T
HUGHES, JL
JONES, JE
机构
[1] SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA
[2] SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA
[3] RW JOHNSON PHARMACEUT RES INST, SAN DIEGO, CA 92121 USA
关键词
HEPATITIS-B VIRUS; TOLERANCE; PERSISTENT INFECTION; AUTOIMMUNITY;
D O I
10.1073/pnas.88.10.4348
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:4348 / 4352
页数:5
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