Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo.
Antigen priming of naive CD4 T cells can generate effector CD4 T cells that produce interleukin 4 (T helper [Th]2-like) or interferon-gamma (Th1-like). Using a system in which priming leads to responses dominated by one or the other of these cell types, we show that varying either the antigenic peptide or the major histocompatibility complex class II molecule can determine whether Th1-like or Th2-like responses are obtained. Our results show that peptide/major histocompatibility complex class II complexes that interact strongly with the T cell receptor favor generation of Th1-like cells, while those that bind weakly favor priming of Th2-like T cells. Thus, signals from the T cell receptor can influence the differentiation of CD4 T cells into specific types of effector cells.
Pfeiffer
C
C
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Stein
J
J
Southwood
S
S
Ketelaar
H
H
Sette
A
A
Bottomly
K
K
D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D002454:Cell Differentiation; D003094:Collagen / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen