A Th1-recognized peptide P277, when tandemly repeated, enhances a Th2 immune response toward effective vaccines against autoimmune diabetes in nonobese diabetic mice.
Subunit immunogens containing tandemly repeated copies of T and B cell epitopes have been shown to be more immunogenic than the respective immunogen containing only a single copy of the sequence. To investigate whether the increased copies of the Th2-activated peptide sequence will enhance the Th2-like immune response, we compared the cytokine secreted in mice that inoculated with two immunogens containing one or six tandemly repeated copies of a Th2-activated peptide sequence P277. Immunization of mice with a 6xP277 fusion protein elicited much higher levels of Th2-type cytokines and lower Th1-type cytokines than with a fusion protein with one P277 peptide. The data of tandemly repeated peptide P277 potentiate the anti-inflammatory in NOD mice, most likely associated with a Th1 to Th2 cytokine shift specific for the autoimmune T cells, which suggested that application of multiple tandem repeats of a Th2-activated epitope is an efficient method to enhance the anti-inflammatory immune response by shifting the immune response from Th1-like to Th2-like. The subunit immunogens containing tandemly repeated copies of peptide P277 might be effective vaccines against autoimmune diabetes in NOD mice.
Jin
Liang
L
Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, People's Republic of China.
Zhu
Aihua
A
Wang
Yu
Y
Chen
Qingmei
Q
Xiong
Qiyan
Q
Li
Jianping
J
Sun
Yunxiao
Y
Li
Taiming
T
Cao
Rongyue
R
Wu
Jie
J
Liu
Jingjing
J
D000818:Animals; D049109:Cell Proliferation; D018834:Chaperonin 60; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D020449:Repetitive Sequences, Amino Acid; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use
D018834:Chaperonin 60; D016207:Cytokines; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014612:Vaccines; C095402:peptide 277, heat shock protein 60