Synthesis of Branched Oxime-Linked Peptide Mimetics of the MUC1 Containing a Universal T-Helper Epitope

2004 ◽  
Vol 10 (24) ◽  
pp. 6353-6360 ◽  
Author(s):  
Gaëlle-Anne Cremer ◽  
Nicole Bureaud ◽  
Dominique Lelièvre ◽  
Véronique Piller ◽  
Friedrich Piller ◽  
...  
Author(s):  
Carlos A. Guzmán ◽  
Daniele Saverino ◽  
Eva Medina ◽  
Daniela Fenoglio ◽  
Birgit Gerstel ◽  
...  

1993 ◽  
Vol 30 (11) ◽  
pp. 961-968 ◽  
Author(s):  
D.Michael Shaw ◽  
Carolynne M. Stanley ◽  
Charalambos D. Partidos ◽  
Michael W. Steward

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Liangliang Jiang ◽  
Tao Jiang ◽  
Jianhua Luo ◽  
Yanliang Kang ◽  
Yue Tong ◽  
...  

Single B cell antibody technology is a method for isolating antigen-specific B cells from human peripheral blood and obtaining antibody genes in developing antibody drugs. However, owing to immune tolerance to autoantigen, human autoantigen-specific B cells are difficult to acquire by conventional single B cell technology. In this study, we constructed a nitrated T-cell epitope named NitraTh by incorporating p-nitrophenylalanine into a universal T helper epitope. NitraTh had enhanced ability to activate CD4+ T cells and can be recognized by CD4+ T cells with different HLA class II haplotypes. This NitraTh can also break immune tolerance to autoantigens, such as human epidermal growth factor receptor 2 (HER2) and cannabinoid receptor 1, and induce strong specific IgM+ B cell responses in vitro. HER2-NitraTh vaccine can also stimulate the generation of HER2-specific IgG+ B cells in human immune system mice, which was established by cotransplanting lymphocytes and autologous dendritic cells in immunodeficient mice. We obtained 30 fully human IgG antibody genes by sorting single B cells from the human immune system mice immunized with HER2-NitraTh vaccine. The analysis of antibody genes showed that sorted B cells underwent the extensive somatic mutation of the antibody genes. We randomly selected eight genes for cloning, six of which expressed antibodies that can bind to HER2. Hence, we provided a convenient and effective method in acquiring fully human antibody genes against self-proteins, which can be used in developing therapeutic antibody drugs.


1997 ◽  
Vol 94 (14) ◽  
pp. 7499-7502 ◽  
Author(s):  
J. van Bergen ◽  
S. P. Schoenberger ◽  
F. Verreck ◽  
R. Amons ◽  
R. Offringa ◽  
...  

1997 ◽  
Vol 34 (16-17) ◽  
pp. 1113-1120 ◽  
Author(s):  
Iben Dalum ◽  
Martin Roland Jensen ◽  
Klaus Gregorius ◽  
Claus Michael Thomasen ◽  
Henrik Irgang Elsner ◽  
...  
Keyword(s):  
T Helper ◽  

1998 ◽  
Vol 187 (5) ◽  
pp. 693-702 ◽  
Author(s):  
Ferry Ossendorp ◽  
Erica Mengedé ◽  
Marcel Camps ◽  
Rian Filius ◽  
Cornelis J.M. Melief

This study shows that induction of tumor-specific CD4+ T cells by vaccination with a specific viral T helper epitope, contained within a synthetic peptide, results in protective immunity against major histocompatibility complex (MHC) class II negative, virus-induced tumor cells. Protection was also induced against sarcoma induction by acutely transforming retrovirus. In contrast, no protective immunity was induced by vaccination with an unrelated T helper epitope. By cytokine pattern analysis, the induced CD4+ T cells were of the T helper cell 1 type. The peptide-specific CD4+ T cells did not directly recognize the tumor cells, indicating involvement of cross-priming by tumor-associated antigen-presenting cells. The main effector cells responsible for tumor eradication were identified as CD8+ cytotoxic T cells that were found to recognize a recently described immunodominant viral gag-encoded cytotoxic T lymphocyte (CTL) epitope, which is unrelated to the viral env-encoded T helper peptide sequence. Simultaneous vaccination with the tumor-specific T helper and CTL epitopes resulted in strong synergistic protection. These results indicate the crucial role of T helper cells for optimal induction of protective immunity against MHC class II negative tumor cells. Protection is dependent on tumor-specific CTLs in this model system and requires cross-priming of tumor antigens by specialized antigen-presenting cells. Thus, tumor-specific T helper epitopes have to be included in the design of epitope-based vaccines.


2000 ◽  
Vol 164 (3) ◽  
pp. 1625-1633 ◽  
Author(s):  
Jeff Alexander ◽  
Marie-France del Guercio ◽  
Ajesh Maewal ◽  
Lei Qiao ◽  
John Fikes ◽  
...  

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