Chen Z W, Shen L, Regan J D, Kou Z, Ghim S H, Letvin N L
Harvard Medical School, Beth Israel Hospital, Boston, MA 02215, USA.
J Immunol. 1996 Feb 15;156(4):1469-75.
MHC class I-restricted CTL play an important role in limiting the spread of HIV-1 in the infected individual. Elucidating the molecular interactions of CTL with the virus is, therefore, of central importance for characterizing the immune control of this infection. In exploring this CTL response, we have defined the TCR usage by SIVmac Gag-specific CTL in rhesus monkeys. Thirty-nine CTL clones were generated from PBL of three SIVmac-infected monkeys expressing the MHC class I Mamu-A01 gene product, all of which were shown to recognize a single SIVmac Gag peptide in association with Mamu-A01. Sixty-six percent of CTL clones derived from two monkeys early after infection expressed TCR genes of the V beta 13 family; 70% of these V beta 13+ CTL clones expressed a TCR heterodimer composed of V alpha 1 and V beta 13 gene products. In addition, there appeared to be a selection of a single conserved amino acid and restricted CDR3 lengths in junctional regions of TCR beta-chains expressed by the V beta 13+ CTL clones. These findings indicate significant structural constraints on the CTL-TCR interaction with the AIDS virus. Interestingly, 55% of the CTL clones derived from the third animal at a later time following infection employed genes of the V beta 6 family in their TCR. Despite the preferential use of TCR V family genes by the CTL clones, the SIVmac Gag-specific CTL response was clearly polyclonal; TCR expressed by these CTL clones displayed varied sequences in their CDR3 regions. Other V gene families, including V beta 23, V alpha 8, and V alpha 20, were used in TCR expressed by SIVmac Gag-specific CTL clones. These studies, therefore, indicate that the TCR repertoire of SIVmac Gag-specific CTL that share a peptide and MHC class I recognition specificity can be diverse. Such a broad CTL-TCR repertoire may be advantageous for the host in containing an AIDS virus infection.
MHC I类限制性细胞毒性T淋巴细胞（CTL）在限制HIV-1在受感染个体中的传播中发挥着重要作用。因此，阐明CTL与病毒的分子相互作用对于表征这种感染的免疫控制至关重要。在探索这种CTL反应时，我们确定了恒河猴中SIVmac Gag特异性CTL的TCR使用情况。从三只表达MHC I类Mamu-A01基因产物的SIVmac感染猴子的外周血淋巴细胞（PBL）中产生了39个CTL克隆，所有这些克隆都被证明能识别与Mamu-A01相关的单一SIVmac Gag肽。感染后早期从两只猴子中获得的CTL克隆中有66%表达Vβ13家族的TCR基因；这些Vβ13 + CTL克隆中有70%表达由Vα1和Vβ13基因产物组成的TCR异二聚体。此外，在Vβ13 + CTL克隆表达的TCRβ链的连接区似乎存在单个保守氨基酸的选择和受限的CDR3长度。这些发现表明CTL-TCR与艾滋病病毒相互作用存在显著的结构限制。有趣的是，感染后较晚时间从第三只动物中获得的CTL克隆中有55%在其TCR中使用Vβ6家族的基因。尽管CTL克隆优先使用TCR V家族基因，但SIVmac Gag特异性CTL反应显然是多克隆的；这些CTL克隆表达的TCR在其CDR3区域显示出不同的序列。其他V基因家族，包括Vβ23、Vα8和Vα20，也被SIVmac Gag特异性CTL克隆表达的TCR所使用。因此，这些研究表明，共享肽和MHC I类识别特异性的SIVmac Gag特异性CTL的TCR库可能是多样的。这样广泛的CTL-TCR库可能对宿主控制艾滋病病毒感染有利。
