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Institut National de la Santé et de la Recherche Médicale, Unité 28, Institut Fédératif de Recherche 30, Hôpital Purpan, Toulouse, France; and
Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale, Unité 277, Institut Pasteur, Paris, France
Although much progress has been made in characterization of the
signaling pathways that control Th cell commitment, little is known
about the early events that govern differentiation of IL-4-producing T
lymphocytes in vivo. We have previously shown that chronic
administration of low dose, soluble hen egg white lysozyme (HEL)
induced the selective development of Ag-specific Th2 in genetically
predisposed BALB/c mice. Here, we show that these memory/effector Th2
cells express a unique TCR V
repertoire, different from the TCR V
profile of primary effector cells from HEL-adjuvant-primed mice. This
Th2-associated repertoire contains a highly frequent public clonotype
characterized by preferred TCR AV and BV gene segment usage along with
conserved sequences in the third hypervariable regions of both TCR
chains. This Th2 clonotype, which is not recruited in primary effector
T cells from HEL-adjuvant-immunized mice, recognized an
IAd-restricted HEL determinant, preferentially processed by
dendritic cells, but not by B cells. Thus, IL-4-producing CD4 T cells
that expand following chronic Ag sensitization emerge from a distinct
pool of precursors, supporting the hypothesis that ligand-TCR
interactions play a crucial role in the regulation of Ag-specific Th2
cell development in vivo.
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