       Document 0414
 DOCN  M9630414
 TI    Myelin proteolipid protein-induced Th1 and Th2 clones express TCR with
       similar fine specificity for peptide and CDR3 homology despite diverse V
       beta usage.
 DT    9603
 AU    van der Veen RC; Chen PJ; McMillan M; Department of Neurology,
       University of Southern California School; of Medicine, Los Angeles
       90033, USA.
 SO    Cell Immunol. 1995 Dec;166(2):291-5. Unique Identifier : AIDSLINE
       GENBANK
 AB    Myelin-specific T-helper (Th) cells which induce encephalomyelitis
       belong to the inflammatory Th1 subset. Th2 cells recognizing similar
       epitopes potentially represent specific inhibitors of encephalitogenic
       Th1 cells. Since the differential stimulation of antigen-specific Th2
       cells may be important in the regulation of autoimmune inflammatory
       disorders, we have examined the fine specificity of a Th1 and a Th2
       clone, induced by immunization of SJL mice with native proteolipid
       protein (PLP) and specific for the PLP 139-151 sequence. Stimulation of
       the clones by synthetic peptides containing single alanine substitutions
       demonstrated that L141, W144, H147, and P148 represent critical
       residues. Surprisingly, this pattern was identical for both subsets.
       Competition studies indicated indirectly that L141 and P148 may be
       MHC-binding residues, whereas W144 and H147 contact the TCR. Sequencing
       of the TCR expressed by both Th subset clones demonstrated different V
       beta usage as well as variation in the D-region sequence and length.
       Interestingly, realignment of the sequence of the CDR3 regions showed
       striking homology. This study demonstrates that Th1 and Th2 subsets can
       express very similar peptide specificities, while utilizing very
       different TCR V beta chains. These results suggest that the therapeutic
       modalities based on either peptide antagonists or antibodies specific
       for CDR3 may have limited effectiveness in treating autoimmune
       disorders, since they may also target the beneficial arm of the immune
       response.
 DE    Amino Acid Sequence  Animal  Base Sequence  Clone Cells  Immunodominant
       Epitopes/*CHEMISTRY/DRUG EFFECTS  Mice  Mice, Inbred Strains  Molecular
       Sequence Data  Myelin Proteolipid Protein/*PHARMACOLOGY  Receptor-CD3
       Complex, Antigen, T-Cell/*CHEMISTRY/DRUG EFFECTS/  GENETICS  Receptors,
       Antigen, T-Cell, alpha-beta/DRUG EFFECTS/GENETICS/  *IMMUNOLOGY
       *Sequence Homology, Amino Acid  *Sequence Homology, Nucleic Acid
       Support, U.S. Gov't, P.H.S.  Th1 Cells/CHEMISTRY/DRUG
       EFFECTS/*IMMUNOLOGY  Th2 Cells/CHEMISTRY/DRUG EFFECTS/*IMMUNOLOGY
       JOURNAL ARTICLE

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

