T CELL MEMORY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在感染HIV等病毒后，抗原从大量T和B细胞中选择特异性淋巴细胞，并诱导它们选择性增殖。这些活化的淋巴细胞促进快速抗原清除，并且在中和病原威胁后，它们作为记忆淋巴细胞在宿主中持续存在一生。最初在接种流感病毒疫苗的人类中描述的“原始抗原罪”现象，作为伯内特的B细胞接合规则的悖论而突出。先前暴露于流感病毒的人在感染新型流感毒株后，产生主要针对旧病毒毒株的抗体，代价是对新型保护性抗原决定簇的应答，从而加剧当前感染的严重性。这种免疫系统的盲点和对“原始抗原”的反应的重定向，而不是对当前病毒中的新表位的反应，是最近报道质疑的现象。因此，我们重新审视了这个问题，以确定变异流感病毒诱导OAS的程度。 使用两种相关的甲型流感病毒株，我们已经表明OAS可以导致免疫记忆和回忆反应的发展显着下降。 此外，我们已经表明，用活流感病毒株连续感染小鼠导致对第一种病毒株的几乎排他性的中和抗体应答，这表明OAS的诱导可能是变异流感病毒破坏免疫系统的潜在策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Following infection with viruses such as HIV, antigens select specific lymphocytes from a large repertoire of T and B cells and induce them to selectively proliferate. These activated lymphocytes facilitate rapid antigen clearance and, upon neutralization of the pathogenic threat, they persist in the host as memory lymphocytes for a lifetime. The phenomenon of "original antigenic sin", first described in humans vaccinated against influenza virus, stands out as a paradox to Burnet's rules of B cell engagement. Humans previously exposed to influenza virus, upon infection with a novel influenza strain, produce antibodies directed primarily against the older viral strains at the expense of responses to novel protective antigenic determinants thus exacerbating the severity of the current infection. This blind spot of the immune system and the redirection of responses to the "original antigen," but not to novel epitopes in the current virus is a phenomenon which recent reports have questioned. Hence, we revisited this issue to determine the extent to which OAS is induced by variant influenza viruses. Using two related strains of influenza A viruses, we have shown that OAS can lead to a significant decrease in the development of immune memory and recall responses. In addition, we have shown that sequential infection of mice with live influenza virus strains leads to almost exclusive neutralizing antibody responses to the first viral strain suggesting that the induction of OAS could be a potential strategy by which variant influenza viruses subvert the immune system.