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M9630087.TXT
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1996-02-27
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Document 0087
DOCN M9630087
TI A delta T-cell receptor deleting element transgenic reporter construct
is rearranged in alpha beta but not gamma delta T-cell lineages.
DT 9603
AU Shutter J; Cain JA; Ledbetter S; Rogers MD; Hockett RD Jr; Department of
Medicine, Howard Hughes Medical Institute,; Washington University School
of Medicine, St. Louis, Missouri; 63110, USA.
SO Mol Cell Biol. 1995 Dec;15(12):7022-31. Unique Identifier : AIDSLINE
MED/96069412
AB T cells can be divided into two groups on the basis of the expression of
either alpha beta or gamma delta T-cell receptors (TCRs). Because the
TCR delta chain locus lies within the larger TCR alpha chain locus,
control of the utilization of these two receptors is important in T-cell
development, specifically for determination of T-cell type:
rearrangement of the alpha locus results in deletion of the delta coding
segments and commitment to the alpha beta lineage. In the developing
thymus, a relative site-specific recombination occurs by which the TCR
delta chain gene segments are deleted. This deletion removes all D
delta, J delta, and C delta genes and occurs on both alleles. This delta
deletional mechanism is evolutionarily conserved between mice and
humans. Transgenic mice which contain the human delta deleting elements
and as much internal TCR delta chain coding sequence as possible without
allowing the formation of a complete delta chain gene were developed.
Several transgenic lines showing recombinations between deleting
elements within the transgene were developed. These lines demonstrate
that utilization of the delta deleting elements occurs in alpha beta T
cells of the spleen and thymus. These recombinations are rare in the
gamma delta population, indicating that the machinery for utilization of
delta deleting elements is functional in alpha beta T cells but absent
in gamma delta T cells. Furthermore, a discrete population of early
thymocytes containing delta deleting element recombinations but not V
alpha-to-J alpha rearrangements has been identified. These data are
consistent with a model in which delta deletion contributes to the
implementation of a signal by which the TCR alpha chain locus is
rearranged and expressed and thus becomes an alpha beta T cell.
DE Animal Base Sequence Comparative Study CD8-Positive
T-Lymphocytes/IMMUNOLOGY DNA Primers Flow Cytometry *Gene Deletion
*Gene Rearrangement, delta-Chain T-Cell Antigen Receptor Human Mice
Mice, Inbred CBA Mice, Inbred C3H Mice, Inbred C57BL Mice, Transgenic
Molecular Sequence Data Polymerase Chain Reaction Receptors, Antigen,
T-Cell, alpha-beta/*BIOSYNTHESIS/GENETICS Receptors, Antigen, T-Cell,
gamma-delta/*BIOSYNTHESIS/GENETICS Spleen/IMMUNOLOGY Support, Non-U.S.
Gov't Support, U.S. Gov't, P.H.S. T-Lymphocyte Subsets/*IMMUNOLOGY
T-Lymphocytes/*IMMUNOLOGY Thymus Gland/IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).