       Document 0142
 DOCN  M95B0142
 TI    Distinct signaling properties identify functionally different CD4
       epitopes.
 DT    9511
 AU    Baldari CT; Milia E; Di Somma MM; Baldoni F; Valitutti S; Telford JL;
       Department of Evolutionary Biology, University of Siena, Italy.
 SO    Eur J Immunol. 1995 Jul;25(7):1843-50. Unique Identifier : AIDSLINE
       MED/95347379
 AB    The CD4 coreceptor interacts with non-polymorphic regions of major
       histocompatibility complex class II molecules on antigen-presenting
       cells and contributes to T cell activation. We have investigated the
       effect of CD4 triggering on T cell activating signals in a lymphoma
       model using monoclonal antibodies (mAb) which recognize different CD4
       epitopes. We demonstrate that CD4 triggering delivers signals capable of
       activating the NF-AT transcription factor which is required for
       interleukin-2 gene expression. Whereas different anti-CD4 mAb or HIV-1
       gp120 could all trigger activation of the protein tyrosine kinases
       p56lck and p59fyn and phosphorylation of the Shc adaptor protein, which
       mediates signals to Ras, they differed significantly in their ability to
       activate NF-AT. Lack of full activation of NF-AT could be correlated to
       a dramatically reduced capacity to induce calcium flux and could be
       complemented with a calcium ionophore. The results identify functionally
       distinct epitopes on the CD4 coreceptor involved in activation of the
       Ras/protein kinase C and calcium pathways.
 DE    Antigen-Antibody Reactions  Antigenic Determinants  Antigens,
       CD4/*IMMUNOLOGY  Calcium/*METABOLISM  Cell Line  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY  DNA-Binding Proteins/*PHYSIOLOGY  Gene
       Expression Regulation  Human  HIV Envelope Protein gp120/IMMUNOLOGY
       *Lymphocyte Transformation  Phosphorylation  Protein-Tyrosine
       Kinase/METABOLISM  Proteins/METABOLISM  Proto-Oncogene
       Proteins/METABOLISM  Receptor Aggregation  *Signal Transduction
       Support, Non-U.S. Gov't  Transcription Factors/*PHYSIOLOGY  JOURNAL
       ARTICLE

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

