Chronic soluble antigen sensitization primes a unique memory/effector T cell repertoire associated with th2 phenotype acquisition in vivo.
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 Vbeta repertoire, different from the TCR Vbeta 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 IA(d)-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.
Foucras
Gilles
G
Institut National de la Santé et de la Recherche Médicale, Unité 28, Institut Fédératif de Recherche 30, Hôpital Purpan, place du Dr. Baylac, 31059 Toulouse, France.
Gallard
Alexandra
A
Coureau
Christiane
C
Kanellopoulos
Jean-M
JM
Guéry
Jean-Charles
JC
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D019674:Genes, T-Cell Receptor beta; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C041136:Ia-like antigens, avian; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; C421864:hen egg lysozyme; D009113:Muramidase