CYTOTOXIC T LYMPHOCYTES IN INFLUENZA VIRUS EVOLUTION

这项研究的长期目标是了解 细胞毒性T淋巴细胞在新型人类甲型流感病毒进化中的作用 在病毒和预防流感病毒感染方面具有重要作用。至 要做到这一点，一组小鼠细胞毒性T淋巴细胞(CTL) H3型人流感病毒血凝素(HA)特异性克隆 病毒就会被准备好。这些克隆将在 识别能力(或无识别能力)的细胞毒性检测 实验室选择的具有已知HA的自然发生的变体 序列，测试它们在体内选择变异体和 在体外，分析I类MHC产品对其影响 特异性，并检查它们减少病毒的能力 感染流感病毒的小鼠的复制和死亡率。 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)及其作用 MHC对HA特异性抗原产生和特异性的限制 CTL；以及(3)确定HA特异性CTL是否具有保护作用 受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和作用 CTL在新流行毒株进化中的作用尚未得到 已定义。更好地理解豁免权的这一方面可能 为未来预防流感等做出贡献 相对于整体而言，信息还具有更广泛的影响 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.