Lewicki H A, Von Herrath M G, Evans C F, Whitton J L, Oldstone M B
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Virology. 1995 Aug 20;211(2):443-50. doi: 10.1006/viro.1995.1426.
The proteins of lymphocytic choriomeningitis virus (LCMV) contain only three known peptide regions that are processed and then held in place by the MHC class I H-2b (Db) glycoprotein on the cell's surface for recognition by LCMV-specific Db-restricted cytotoxic T lymphocytes (CTL). These peptides are from the glycoprotein (GP), amino acids 33-41 KAVYNFATC (GP1) and 276-286 SGVENPGGYCL (GP2), and the nucleoprotein (NP), 396-404. We have used CTL clones that recognized only GP1, GP2, and NP to select viral variants that upon infecting cells bearing H-2b molecules escaped recognition by virus-specific CTL directed against the viral GP (GP1 + GP2) mutant, termed GPV, or the viral GP and NP (GP1 + GP2 + NP) mutant, termed GPV+NPV. These CTL "escape" variants nevertheless elicited sufficient host-protective activity in vivo to abort acute infection and prevent the occurrence of persistent infection. This protection was CD8+ lymphocyte mediated and associated with the generation of a novel (for H-2b mice) CTL response to the viral L protein. Hence CTL epitopes form a hierarchy, in which responses to "weak" epitopes are suppressed in the presence of "stronger" epitopes. Mutation in the strong epitopes may be of limited biological significance since the host can mount a protective response directed against the second level (weak) epitopes.
淋巴细胞性脉络丛脑膜炎病毒（LCMV）的蛋白质仅包含三个已知的肽区域，这些区域经过加工后，由细胞表面的MHC I类H-2b（Db）糖蛋白固定在原位，以供LCMV特异性Db限制性细胞毒性T淋巴细胞（CTL）识别。这些肽来自糖蛋白（GP），氨基酸33 - 41 KAVYNFATC（GP1）和276 - 286 SGVENPGGYCL（GP2），以及核蛋白（NP），396 - 404。我们使用仅识别GP1、GP2和NP的CTL克隆来选择病毒变体，这些变体在感染携带H-2b分子的细胞后，能够逃避针对病毒GP（GP1 + GP2）突变体（称为GPV）或病毒GP和NP（GP1 + GP2 + NP）突变体（称为GPV+NPV）的病毒特异性CTL的识别。然而，这些CTL“逃逸”变体在体内引发了足够的宿主保护活性，以中止急性感染并防止持续性感染的发生。这种保护是由CD8 +淋巴细胞介导的，并且与对病毒L蛋白产生新的（对于H-2b小鼠而言）CTL反应相关。因此，CTL表位形成了一个层次结构，其中在存在“更强”表位的情况下，对“弱”表位的反应会受到抑制。强表位的突变可能具有有限的生物学意义，因为宿主可以针对二级（弱）表位产生保护性反应。
