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https://doi.org/10.1371/journal.pone.0006811
Title: | Enhancement of tumour-specific immune responses in vivo by 'MHC loading-enhancer' (MLE) | Authors: | Dickhaut K. Hoepner S. Eckhard J. Wiesmueller K.-H. Schindler L. Jung G. Falk K. Roetzschke O. |
Keywords: | adamantane HLA DR antigen HLA DR1 antigen HLA DR4 antigen major histocompatibility antigen major histocompatibility antigen class 2 NY ESO 1 antigen tumor antigen cancer vaccine HLA antigen class 2 subunit vaccine animal cell animal experiment animal model antibody combining site antigen presenting cell article catalysis CD4+ T lymphocyte controlled study dendritic cell immune response in vivo study Influenza virus ligand binding mouse nonhuman transgenic mouse animal Bagg albino mouse cell proliferation cell separation chemistry CpG island human immunology immunotherapy methodology neoplasm tumor cell line Murinae Mus Orthomyxoviridae Animals Cancer Vaccines CD4-Positive T-Lymphocytes Cell Line, Tumor Cell Proliferation Cell Separation CpG Islands Histocompatibility Antigens Class II Humans Immunotherapy Mice Mice, Inbred BALB C Mice, Transgenic Neoplasms Vaccines, Subunit |
Issue Date: | 2009 | Citation: | Dickhaut K., Hoepner S., Eckhard J., Wiesmueller K.-H., Schindler L., Jung G., Falk K., Roetzschke O. (2009). Enhancement of tumour-specific immune responses in vivo by 'MHC loading-enhancer' (MLE). PLoS ONE 4 (9) : e6811. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0006811 | Rights: | Attribution 4.0 International | Abstract: | Background: Class II MHC molecules (MHC II) are cell surface receptors displaying short protein fragments for the surveillance by CD4+ T cells. Antigens therefore have to be loaded onto this receptor in order to induce productive immune responses. On the cell surface, most MHC II molecules are either occupied by ligands or their binding cleft has been blocked by the acquisition of a non-receptive state. Direct loading with antigens, as required during peptide vaccinations, is therefore hindered. Principal Findings: Here we show, that the in vivo response of CD4+ T cells can be improved, when the antigens are administered together with 'MHC-loading enhancer' (MLE). MLE are small catalytic compounds able to open up the MHC binding site by triggering ligand-release and stabilizing the receptive state. Their enhancing effect on the immune response was demonstrated here with an antigen from the influenza virus and tumour associated antigens (TAA) derived from the NYESO-1 protein. The application of these antigens in combination with adamantane ethanol (AdEtOH), an MLE compound active on human HLA-DR molecules, significantly increased the frequency of antigen-specific CD4+ T cells in mice transgenic for the human MHC II molecule. Notably, the effect was evident only with the MLE-susceptible HLA-DR molecule and not with murine MHC II molecules non-susceptible for the catalytic effect of the MLE. Conclusion: MLE can specifically increase the potency of a vaccine by facilitating the efficient transfer of the antigen onto the MHC molecule. They may therefore open a new way to improve vaccination efficacy and tumour-immunotherapy. � 2009 Dickhaut et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161829 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0006811 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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