Document 0775
 DOCN  M9440775
 TI    Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe
       combined immunodeficiency disease result in the loss of high-affinity
       IL-2 receptor binding.
 DT    9404
 AU    DiSanto JP; Dautry-Varsat A; Certain S; Fischer A; de Saint Basile G;
       INSERM U132, Hopital Necker-Enfants Malades, Paris, France.
 SO    Eur J Immunol. 1994 Feb;24(2):475-9. Unique Identifier : AIDSLINE
       MED/94130970
 AB    Interactions of interleukin-2 (IL-2) with its high-affinity,
       heterotrimeric receptor (IL-2R alpha beta gamma) play a pivotal role in
       the autocrine pathway of T lymphocyte expansion required in an immune
       response. Mutations in the IL-2R gamma chain-encoding gene have been
       found in SCIDX1, a primary immunodeficiency characterized by the absence
       of T cell and NK cell development. We have investigated six unrelated
       SCIDX1 patients for molecular abnormalities of the IL-2R gamma gene. A
       variety of defects were identified, including the absence of
       transcripts, frame-shift deletions and point mutations within canonical
       cytokine receptor motifs (conserved cysteines and the WS box). The
       ability of these mutated IL-2R gamma chains to participate in the
       function of a high-affinity IL-2R complex was examined by radiolabeled
       IL-2 binding studies using Epstein-Barr virus-transformed B
       lymphoblastoid cell lines (B-LCL) derived from SCIDX1 patients. Although
       normal control B-LCL express high-affinity IL-2 binding sites (Kd = 60
       pM, 150 sites/cell), B-LCL derived from SCIDX1 patients failed to bind
       IL-2 under high-affinity conditions. These SCIDX1 mutations confirm the
       critical role of the IL-2R gamma chain in T cell and NK cell
       development. In addition, these data provide insight into the
       structure/function relationship of the IL-2R gamma chain by identifying
       residues required for the formation of a high-affinity IL-2R complex.
 DE    Base Sequence  DNA Primers/CHEMISTRY  Human  Molecular Sequence Data
       Point Mutation  Receptors, Interleukin-2/*GENETICS/METABOLISM  RNA,
       Messenger/GENETICS  Severe Combined
       Immunodeficiency/GENETICS/*IMMUNOLOGY  Support, Non-U.S. Gov't  X
       Chromosome  JOURNAL ARTICLE

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