Shen L, Chen Z W, Letvin N L
Harvard Medical School, Beth Israel Hospital, Boston, MA 02215.
J Immunol. 1994 Dec 15;153(12):5849-54.
The importance of the repertoire of a primed, AIDS virus-specific population of CTL in the recognition of emerging mutant viruses was assessed in simian immunodeficiency virus (SIV)-infected rhesus monkeys. These studies were done by using the well-characterized CTL recognition of the SIVmac Gag peptide 11C (p11C) epitope in rhesus monkeys expressing the MHC class I molecule Mamu-A01. Lysis of peptide-pulsed targets by bulk PBL effector cells from SIVmac-infected, Mamu-A01+ monkeys was significantly decreased by mutations at residues 2, 3, and 5 of the nine-amino-acid Gag p11C epitope. However, effector cell lysis of targets pulsed with p11C containing substitutions at residues 3 or 5 was substantially increased by in vitro incubation of the monkeys' PBL with these mutant peptides. This suggested that expandable populations of cells exist in the primed CTL of infected monkeys capable of recognizing mutant peptide sequences. In fact, without in vitro exposure of PBL to mutant peptides, SIVmac Gag-specific CTL could be cloned from PBL of infected monkeys that lysed targets pulsed with mutant peptides. These observations suggest that clones of effector cells capable of recognizing many viral mutants may be able to expand in vivo to control the spread of emerging variant AIDS viruses.
在感染猿猴免疫缺陷病毒（SIV）的恒河猴中，评估了经致敏的、艾滋病病毒特异性CTL群体的库在识别新出现的突变病毒方面的重要性。这些研究通过在表达MHC I类分子Mamu-A01的恒河猴中利用对SIVmac Gag肽11C（p11C）表位的充分表征的CTL识别来进行。来自感染SIVmac、Mamu-A01+的猴子的大量PBL效应细胞对肽脉冲靶标的裂解作用因九氨基酸Gag p11C表位的第2、3和5位残基处的突变而显著降低。然而，通过将猴子的PBL与这些突变肽进行体外孵育，用在第3或5位残基处含有替代物的p11C脉冲的靶标的效应细胞裂解作用大幅增加。这表明在感染猴子的致敏CTL中存在能够识别突变肽序列的可扩增细胞群体。事实上，在没有将PBL体外暴露于突变肽的情况下，能够从感染猴子的PBL中克隆出裂解用突变肽脉冲的靶标的SIVmac Gag特异性CTL。这些观察结果表明，能够识别许多病毒突变体的效应细胞克隆可能能够在体内扩增以控制新出现的变异艾滋病病毒的传播。
