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1996-03-04
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Document 0597
DOCN M9640597
TI Preferential positive selection of T lymphocytes which express two
different TCR alpha chains, an endogenous and a transgenic.
DT 9604
AU Munthe LA; Sollien A; Dembic Z; Bogen B; Institute of Immunology and
Rheumatology, University of Oslo,; Norway.
SO Scand J Immunol. 1995 Dec;42(6):651-61. Unique Identifier : AIDSLINE
MED/96150315
AB A hallmark of positive selection in T-cell receptor (TCR)-transgenic
mice is a strong skewing towards the CD4+ or the CD8+ subset, depending
on the class II or I restriction of the TCR, respectively. However,
previous experiments in TCR transgenic mice specific for an Ig light
chain (lambda 2(315)/I-Ed class II molecule did not fit into this scheme
because the authors observed an anomalous skewing towards CD8. In this
paper the authors show that endogenous TCR alpha chains are expressed on
> 90% of CD4+ and CD8+ cells in this particular transgenic strain, even
on a selecting H-2d haplotype. Endogenous TCR alpha chains are first
detected when double-positive thymocytes down-regulate either CD4 or
CD8. Endogenous V alpha seems to influence generation of T-cell subsets
because CD4+ and CD8+ cells express different frequencies of endogenous
V alpha 2 and V alpha 8. In the absence of endogenous TCR alpha chains
in recombination-deficient TCR-transgenic severe combined
immunodeficiency (SCID) mice, a strong skewing towards CD4+ T cells is
seen, but such mice are severely T-cell deficient. As an explanation for
these results, the authors suggest that the transgenic TCR has a too low
affinity for efficient positive selection, therefore, TCR alpha gene
rearrangements proceed. Endogenous TCR alpha paired with transgenic TCR
beta could bind to class I or class II molecules, enhance positive
selection and thereby production of CD4+ or CD8+ cells. Most of the
'mismatched' CD8+ cells are lambda 2(315)-specific and I-Ed class II
restricted, and may function as idiotype-specific suppressors of B
cells. These results may help explain the origin of dual TCR alpha T
cells. Furthermore, the authors suggest that T cells 'mismatched' for
co-receptor/TCR MHC-specificity may be enriched among dual TCR alpha T
cells.
DE Animal Cell Differentiation Clonal Deletion Clone Cells CD4-Positive
T-Lymphocytes/CYTOLOGY/IMMUNOLOGY CD8-Positive
T-Lymphocytes/CYTOLOGY/IMMUNOLOGY H-2 Antigens/IMMUNOLOGY
Immunoglobulins, Light-Chain/IMMUNOLOGY Mice Mice, Inbred BALB C
Mice, Transgenic Receptors, Antigen, T-Cell,
alpha-beta/*BIOSYNTHESIS/GENETICS Support, Non-U.S. Gov't T-Lymphocyte
Subsets/CYTOLOGY/*IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).