Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Generation and characterization of high affinity human monoclonal antibodies that neutralize staphylococcal enterotoxin cytokines by bridging the MHC II molecules | Drozdowski et al. Journal of Immune Based Therapies and Vaccines 2010 8 9 http content 8 1 9 JOURNAL OF IMMUNE BASED THERAPIES AND VACCINES ORIGINAL RESEARCH Open Access Generation and characterization of high affinity human monoclonal antibodies that neutralize staphylococcal enterotoxin B 1 1 1 1 z I 1 1 1 Brian Drozdowski Yuhong Zhou Brad Kline Jared Spidel Yin Yin Chan Earl Albone Howard Turchin 1 1 1 1 2 1 Qimin Chao Marianne Henry Jacqueline Balogach Eric Routhier Sina Bavari Nicholas C Nicolaides Philip M Sass1 Luigi Grasso1 Abstract Background Staphylococcal enterotoxins are considered potential biowarfare agents that can be spread through ingestion or inhalation. Staphylococcal enterotoxin B SEB is a widely studied superantigen that can directly stimulate T-cells to release a massive amount of proinflammatory cytokines by bridging the MHC II molecules on an antigen presenting cell APC and the Vb chains of the T-cell receptor TCR . This potentially can lead to toxic debilitating and lethal effects. Currently there are no preventative measures for SEB exposure only supportive therapies. Methods To develop a potential therapeutic candidate to combat SEB exposure we have generated three human B-cell hybridomas that produce human monoclonal antibodies HuMAbs to SEB. These HuMAbs were screened for specificity affinity and the ability to block SEB activity in vitro as well as its lethal effect in vivo. Results The high-affinity HuMAbs as determined by BiaCore analysis were specific to SEB with minimal crossreactivity to related toxins by ELISA. In an immunoblotting experiment our HuMAbs bound SEB mixed in a cell lysate and did not bind any of the lysate proteins. In an in vitro cell-based assay these HuMAbs could inhibit SEB-induced secretion of the proinflammatory cytokines INF-y and TNF-a by primary human lymphocytes with high potency. In an in vivo LPS-potentiated mouse model our lead antibody HuMAb-154 was capable of neutralizing up to .
