       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).

