CYTOTOXIC T LYMPHOCYTES IN INFLUENZA VIRUS EVOLUTION

本研究的长期目标是了解 细胞毒性T淋巴细胞在新型人A型流感病毒演变中的作用 病毒和保护免受流感病毒感染。 到 为了实现这一点，一组鼠细胞毒性T淋巴细胞（CTL） 对H3人流感的血凝素（HA）具有特异性的克隆 将准备一种病毒。 这些克隆将在 细胞毒性测定其识别（或不识别） 具有已知HA的实验室选择的和天然存在的变体 序列，测试它们在体内选择变体的能力， 在体外，分析I类MHC产物对它们的作用。 特异性，并检查它们减少病毒能力 在感染流感病毒的小鼠中的复制和死亡率。 这些数据将用于：（1）确定CTL识别 HA分子上的位点：（2）评估CTL在抗原性中的作用。 流感病毒的变异（漂移和转移）以及 MHC对HA特异性抗原的产生和特异性的限制 CTL;和（3）确定HA特异性CTL是否保护免于 感染动物的发病率和死亡率。 甲型流感病毒 在世界范围内产生重大疾病问题， 尚未发现新流行毒株进化中的CTL作用 定义了 更好地理解免疫的这一方面， 有助于今后预防流感等 信息也有更广泛的影响，相对于， T细胞在宿主防御中的作用

The long-term objective of this study is to understand the role of cytotoxic T lymphocytes in the evolution of new human influenza A viruses and in protection against influenza virus infection. To accomplish this, a panel of murine cytotoxic T lymphocyte (CTL) clones specific for the hemagglutinin (HA) of an H3 human influenza A virus will be prepared. These clones will be analyzed in cytotoxicity assays for their ability (or inability) to recognize laboratory-selected and naturally-occurring variants with known HA sequences, tested for their capacity to select variants in vivo and in vitro, analyzed for the effect of class I MHC products on their specificity, and examine for their ability to reduce virus replication and mortality in mice infected with influenza viruses. These data will be used to: (1) determine the CTL recognition sites on the HA molecule: (2) evaluate the role of CTL in antigenic variation (drift and shift) in influenza viruses and the role of MHC restriction on the generation and specificity of HA-specific CTL; and (3) establish whether HA-specific CTL protect against morbidity and mortality in infected animals. Influenza A viruses produce major disease problems throughout the world and the role of CTL in the evolution of new epidemic strains has not been defined. A better understanding of this aspect of immunity may contribute to the future prevention of influenza and such information also has broader implications, vis-a-vis, the overall role of T cells in host defense.