       Document 0685
 DOCN  M9640685
 TI    The extracellular domain of CD45 controls association with the CD4-T
       cell receptor complex and the response to antigen-specific stimulation.
 DT    9604
 AU    Leitenberg D; Novak TJ; Farber D; Smith BR; Bottomly K; Howard Hughes
       Medical Institute, Section of Immunobiology, Yale; University School of
       Medicine, New Haven, Connecticut 06510, USA.
 SO    J Exp Med. 1996 Jan 1;183(1):249-59. Unique Identifier : AIDSLINE
       MED/96136767
 AB    The CD45 tyrosine phosphatase plays an important role in regulating T
       lymphocyte activation, but the function of the different isoforms of
       CD45 is not known. T cell transfectants have been prepared that express
       individual CD45 isoforms in cells with a well-defined T cell receptor
       (TCR) from the D10 T helper 2 clone. We find that cells bearing low
       molecular weight CD45 isoforms are far more efficient in responding to
       stimulation with peptide and antigen-presenting cells compared with
       cells bearing high molecular weight CD45 isoforms. One hypothesis for
       the preferential activation of cells that express low molecular weight
       CD45 isoforms is that they interact with other cell surface antigens
       important in TCR signaling, altering their phosphorylation status and
       affecting the character of the signal transduction pathway. In this
       report, using cells expressing single isoforms, we demonstrate that low
       molecular weight isoforms of CD45 preferentially associate with CD4 and
       the TCR complex compared with high molecular weight isoforms. The
       molecular basis for this interaction was further examined using a
       glycosyl phosphatidyl inositol (GPI)-linked form of CD45Null (lacking
       tyrosine phosphatase domains), which preferentially associated with CD4
       compared with GPI-linked CD45ABC, and cytoplasmic tail mutants of CD4,
       which retained the ability to coassociate. Using this panel of
       transfectants, it is clear that the interaction between CD4 and CD45
       does not require the cytoplasmic domains of CD45, but is dependent on
       the specific external domain of the various isoforms: low molecular
       weight species were more likely to associate with the CD4-TCR complex
       than the higher molecular weight isoforms, and their ability to
       coassociate correlated with the magnitude of the response to specific
       antigen.
 DE    Amino Acid Sequence  *Antigen Presentation  Antigens, CD4/*METABOLISM
       Antigens, CD45/GENETICS/*METABOLISM  Base Sequence  Cell Line
       Comparative Study  CD4-Positive T-Lymphocytes  CD8-Positive
       T-Lymphocytes  Flow Cytometry  Immunologic Capping  *Lymphocyte
       Transformation  Molecular Sequence Data  Phenotype  Phosphoric Diester
       Hydrolases  Protein Binding  Receptors, Antigen, T-Cell/*METABOLISM
       Recombinant Proteins/METABOLISM  Structure-Activity Relationship
       Support, Non-U.S. Gov't  Transfection  JOURNAL ARTICLE

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

