The role of antigenic peptide in CD4+ T helper phenotype development in a T cell receptor transgenic model.
CD4+ Th1 cells play a critical role in the induction of cell-mediated immune responses that are important for the eradication of intracellular pathogens. Peptide-25 is the major Th1 epitope for Ag85B of Mycobacterium tuberculosis and is immunogenic in I-Ab mice. To elucidate the role of the TCR and IFN-gamma/IL-12 signals in Th1 induction, we generated TCR transgenic mice (P25 TCR-Tg) expressing TCR alpha- and beta-chains of Peptide-25-reactive cloned T cells and analyzed Th1 development of CD4+ T cells from P25 TCR-Tg. Naive CD4+ T cells from P25 TCR-Tg differentiate into both Th1 and Th2 cells upon stimulation with anti-CD3. Naive CD4+ T cells from P25 TCR-Tg preferentially develop Th1 cells upon Peptide-25 stimulation in the presence of I-Ab splenic antigen-presenting cells under neutral conditions. In contrast, a mutant of Peptide-25 can induce solely Th2 differentiation. Peptide-25-induced Th1 differentiation is observed even in the presence of anti-IFN-gamma and anti-IL-12. Furthermore, naive CD4+ T cells from STAT1 deficient P25 TCR-Tg also differentiate into Th1 cells upon Peptide-25 stimulation. Moreover, Peptide-25-loaded I-Ab-transfected Chinese hamster ovary cells induce Th1 differentiation of naive CD4+ T cells from P25 TCR-Tg in the absence of IFN-gamma or IL-12. These results imply that interaction between Peptide-25/I-Ab and TCR may primarily influence determination of the fate of naive CD4+ T cells in their differentiation towards the Th1 subset.
Tamura
Toshiki
T
Division of Immunology, Institute of Medical Science, University of Tokyo, Japan.
Ariga
Haruyuki
H
Kinashi
Tatsuo
T
Uehara
Shuichiro
S
Kikuchi
Takeshi
T
Nakada
Makiyo
M
Tokunaga
Takeshi
T
Xu
Wen
W
Kariyone
Ai
A
Saito
Takashi
T
Kitamura
Toshio
T
Maxwell
Gavin
G
Takaki
Satoshi
S
Takatsu
Kiyoshi
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000494:pharmacology / Q000502:physiology*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology
D000942:Antigens, Bacterial; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D016056:Immunodominant Epitopes; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; C052242:alpha antigens, Mycobacterium; D018664:Interleukin-12; D007371:Interferon-gamma