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Laboratory of Immunobiology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115
To examine the function of CD2 in vivo, N15 TCR transgenic (tg)
RAG-2-/- H-2b mice bearing a single TCR
specific for the vesicular stomatitis virus octapeptide bound to the
H-2Kb molecule were compared on a wild-type or
CD2-/- background. In N15tg RAG-2-/-
CD2-/- mice, thymic dysfunction is evident by 6 wk with a
pre-TCR block in the CD4-CD8- double-negative
thymocytes at the CD25+CD44- stage. Moreover,
mature N15tg RAG-2-/- CD2-/- T cells are
100-fold less responsive to vesicular stomatitis virus octapeptide
and unresponsive to weak peptide agonists, as judged by IFN-
production. Repertoire analysis shows substantial differences in V
usage between non-tg C57BL/6 (B6) and B6 CD2-/- mice.
Collectively, these findings show that CD2 plays a role in pre-TCR
function in double-negative thymocytes, TCR selection events during
thymocyte development, and TCR-stimulated cytokine production in mature
T cells.
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