       Document 0813
 DOCN  M9620813
 TI    Low avidity recognition of self-antigen by T cells permits escape from
       central tolerance.
 DT    9602
 AU    Liu GY; Fairchild PJ; Smith RM; Prowle JR; Kioussis D; Wraith DC;
       Cambridge University Department of Pathology, England.
 SO    Immunity. 1995 Oct;3(4):407-15. Unique Identifier : AIDSLINE
       MED/96036617
 AB    The immunodominant epitope of myelin basic protein, Ac1-9, is
       encephalitogenic in H-2u mice. We have previously demonstrated that this
       epitope displays low affinity for I-Au and have suggested that the
       avidity of T cell recognition in the thymus may be compromised, enabling
       autoreactive T cells to escape self-tolerance. We have addressed this
       hypothesis directly by constructing transgenic mice expressing an
       encephalitogenic T cell receptor (TCR). Parenteral administration of
       Ac1-9 had no discernable impact on developing thymocytes. In contrast,
       peptide analogs displaying far higher affinity for I-Au, provoked
       deletion of CD4+ CD8+ cells and transient down-regulation of the TCR by
       mature CD4+ CD8- thymocytes. The use of analogs of intermediate affinity
       permitted a margin of error to be defined for the induction of tolerance
       and confirmed that the affinity of Ac1-9 lies well below the critical
       threshold.
 DE    Animal  Antibody Affinity  Autoantigens/*IMMUNOLOGY  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY  CD8-Positive T-Lymphocytes/*IMMUNOLOGY
       Encephalomyelitis, Allergic/IMMUNOLOGY  *Immune Tolerance  Lymphocyte
       Transformation  Mice  Mice, Transgenic  Myelin Basic
       Proteins/*IMMUNOLOGY  Receptors, Antigen, T-Cell/GENETICS/*IMMUNOLOGY
       Support, Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

