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Preferential Positive Selection of T Lymphocytes which Express Two Different TCRα Chains, an Endogenous and a Transgenic
Author(s) -
MUNTHE L. A.,
SOLLIEN A.,
DEMBIC Z.,
BOGEN B.
Publication year - 1995
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1995.tb03708.x
Subject(s) - t cell receptor , cd8 , transgene , biology , endogeny , negative selection , t cell , microbiology and biotechnology , genetically modified mouse , cytotoxic t cell , immunology , antigen , genetics , gene , immune system , in vitro , biochemistry , genome
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 (λ2 315 )/I‐E d 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 TCRα chains are expressed on > 90% of CD4 + and CDS + cells in this particular transgenic strain, even on a selecting H‐2 d haplotype. Endogenous TCRQ chains are first detected when double‐positive thymocytes down‐regulate either CD4 or CD8. Endogenous Vα seems to influence generation of T‐cell subsets because CD4 + and CD8 + cells express different frequencies of endogenous Vα2 and Vα8. In the absence of endogenous TCRα 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, TCRa gene rearrangements proceed. Endogenous TCRa paired with transgenic TCRβ 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 λ2 315 ‐specific and I‐E d class II restricted, and may function as idiotype‐specific suppressors of B cells. These results may help explain the origin of dual TCRα T cells. Furthermore, the authors suggest that T cells ‘mismatched’ for co‐receptor/TCR MHC‐specificity may be enriched among dual TCRa T cells.