Induction of in vivo helper activity for murine antibody responses by macrophages pulsed with ovalbumin-monomethoxypolyethylene glycol (OA-mPEG) conjugates |
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| Authors: | V Holford-Strevens C J Jackson J Charlton K A Akiyama G M Lang B G Carter A H Sehon |
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| Affiliation: | 1. MRC Group for Allergy Research, Department of Immunology, The University of Manitoba, Winnipeg, MB, Canada R3E 0W3;2. MRC Group for Allergy Research, Department of Chemistry, The University of Manitoba, Winnipeg, MB, Canada R3E 0W3;1. Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand;2. Department of Chemistry, Faculty of Science, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand;3. Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;4. Department of Clinical Science and Public Health, Faculty of Veterinary Science, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand;5. Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand;6. Department of Pre-clinic and Applied Animal Science, Faculty of Veterinary Science, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand;1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands;2. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands;1. Grupo de Sanidad Animal, INTA Marcos Juárez, Córdoba, Argentina;2. Instituto de Biotecnología Ambiental y Salud (INBIAS), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina;3. Instituto de Agrobiotecnología y Biología Molecular (IABIMO), UEDD INTA-CONICET, CICVyA, Hurlingham, Buenos Aires, Argentina;4. IITEMA CONICET-UNRC, Río Cuarto, Córdoba, Argentina;5. CMC, ICIVET-Litoral, UNL-CONICET, Esperanza, Argentina;6. INCIVET CONICET-UNRC, Rio Cuarto, Argentina |
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| Abstract: | Conjugates of protein antigens with an optimal number of monomethoxypolyethylene glycol (mPEG) chains of an appropriate molecular weight had been shown to suppress murine IgE responses to the unmodified antigen. To investigate the possibility that the tolerogenic capacity of these mPEG conjugates is attributable to a defect in macrophage (M phi) presentation of their antigenic determinants, the activity of ovalbumin (OA)-mPEG conjugates when pulsed onto mouse peritoneal adherent cells (M phi) was compared in this study with their activity in solution. Surprisingly, in contrast to the suppressogenic capacity of mPEG conjugates in solution, the OA-mPEG pulsed M phi appeared to exert a helper effect when injected intraperitoneally (ip), i.e., after subsequent immunization with dinitrophenylated OA (DNP3-OA) in Al(OH)3, the mice showed accelerated IgE and IgG1 antibody responses to OA and DNP. However, when M phi were exposed to limiting concentrations of OA or OA-mPEG, markedly higher concentrations of OA-mPEG were required to yield pulsed M phi, exerting a significant helper effect. It was concluded that although M phi were capable of presenting the OA determinants of OA-mPEG conjugates to helper T (Th) cells, the preparations of modified antigen were presented less effectively than native OA. |
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