A DNA adjuvant encoding a fusion protein between anti-CD3 single-chain Fv and AIMP1 enhances T helper type 1 cell-mediated immune responses in antigen-sensitized mice.
T helper type 1 (Th1) cell-mediated immune responses contribute to host defences against intracellular pathogen infections and cancer. Previously, we found that aminoacyl tRNA synthetase-interacting multifunctional protein 1 (AIMP1) activated macrophages and dendritic cells to enhance Th1 responses. Herein, we manipulated this property to improve Th1 immune responses in vivo by constructing a mammalian expression plasmid (pAnti-CD3sFv/AIMP1) encoding AIMP1 fused to the anti-CD3 single-chain Fv (sFv), the smallest unit of the antibody that interacts with the CD3epsilon region of the T-cell receptor. Intramuscular injection of ovalbumin (OVA)-sensitized BALB/c mice with pAnti-CD3sFv/AIMP1 DNA adjuvant increased the OVA-specific, interferon-gamma production by their CD4(+) T cells and the levels of anti-OVA immunoglobulin G2a (IgG2a) isotype in their sera. Furthermore, the pAnti-CD3sFv/AIMP1 DNA adjuvant decreased interleukin-4 production and anti-OVA IgE levels in the OVA-injected mice. Importantly, the pAnti-CD3sFv/AIMP1 was more efficient than a mixture of pAnti-CD3sFv and pAIMP1 in inducing OVA-specific Th1 immune responses and also in inhibiting OVA-specific Th2 responses during antigen priming. These studies indicated that the pAnti-CD3sFv/AIMP1 fusion DNA adjuvant enhanced Th1 immune responses in antigen-sensitized mice.
School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Byeong Cheol
BC
Lee
Insug
I
O'Sullivan
Eugene
E
Kim
Sang Gyu
SG
Park
Seung Yong
SY
Hwang
Daeho
D
Cho
Tae Sung
TS
Kim
D000276:Adjuvants, Immunologic; D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007273:Injections, Intramuscular; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; C514492:Aimp1 protein, mouse; D017252:CD3 Complex; D016207:Cytokines; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D004247:DNA