Cole G A, Hogg T L, Coppola M A, Woodland D L
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
J Immunol. 1997 May 1;158(9):4301-9.
The relationship between the primary effector CTL response to viral infection and the subsequent pool of memory CTL precursors (CTLp) is poorly understood. Here, we have analyzed the induction of both effector CTL and memory CTLp to dominant and subdominant epitopes following Sendai virus infection of C57BL/6 mice. A single peptide derived from the Sendai virus nucleoprotein (NP(324-332)) binds to both H-2 Kb and Db MHC class I molecules, generating both immunodominant (NP(324-332)/Kb) and subdominant (NP(324-332)/Db) epitopes. Following intranasal Sendai virus infection, NP(324-332)/Kb-specific CTL dominated the primary effector CTL response in the lung and were present at high frequency in the memory CTLp pool. In contrast, NP(324-332)/Db-specific CTL were not a detectable component of the effector response to primary Sendai virus infection. However, memory CTLp specific for this subdominant epitope were induced at frequencies approaching those of CTLp specific for the immunodominant epitope. These data indicate that memory CTLp specific for subdominant epitopes can be primed by Sendai virus infection in the absence of a detectable effector response. To determine whether CTLp memory to subdominant epitopes is functional in the context of Sendai virus infection, memory CTLp specific for a subdominant epitope were selectively primed by vaccination. These cells dominated the subsequent effector CTL response to Sendai virus infection, demonstrating that memory CTLp primed against subdominant epitopes can participate in an immune response and effectively compete with T cells specific for immunodominant epitopes. These data have implications for the development of vaccines designed to emphasize cellular immunity.
对病毒感染的主要效应性细胞毒性T淋巴细胞（CTL）反应与随后的记忆性CTL前体细胞（CTLp）库之间的关系，人们了解甚少。在此，我们分析了C57BL/6小鼠感染仙台病毒后，效应性CTL和记忆性CTLp对显性和隐性表位的诱导情况。源自仙台病毒核蛋白的单个肽段（NP(324 - 332)）可与H - 2 Kb和Db I类主要组织相容性复合体（MHC）分子结合，产生免疫显性表位（NP(324 - 332)/Kb）和隐性表位（NP(324 - 332)/Db）。经鼻内感染仙台病毒后，NP(324 - 332)/Kb特异性CTL在肺部的主要效应性CTL反应中占主导地位，且在记忆性CTLp库中高频存在。相比之下，NP(324 - 332)/Db特异性CTL并非对初次仙台病毒感染的效应性反应中可检测到的成分。然而，针对这种隐性表位的记忆性CTLp以接近针对免疫显性表位的CTLp的频率被诱导产生。这些数据表明，在没有可检测到的效应性反应的情况下，仙台病毒感染可启动针对隐性表位的记忆性CTLp。为了确定针对隐性表位的CTLp记忆在仙台病毒感染背景下是否具有功能，通过疫苗接种选择性地启动了针对隐性表位的记忆性CTLp。这些细胞在随后对仙台病毒感染的效应性CTL反应中占主导地位，表明针对隐性表位启动的记忆性CTLp可参与免疫反应，并能有效地与针对免疫显性表位的T细胞竞争。这些数据对旨在强调细胞免疫的疫苗开发具有启示意义。
