Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H
Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H
复制标题
DOI：
10.1002/eji.200425203
复制
发表时间：
2004-11-01
影响因子：
5.4
通讯作者：
Khanna, R
中科院分区：
文献类型：
--
作者：
Elkington, R;Shoukry, NH;Khanna, R
虽然CD4(+) T细胞对人细胞阴性病毒（HCMV）反应的重要性最近在移植和免疫抑制患者中得到了认识，但这种反应的确切特异性和性质在很大程度上仍未得到解决。在本研究中，我们分离了识别HCMV糖蛋白gB和gH与两种不同HLA-DR抗原DRA1*0101/DRB1*0701 （DR7）和DRA1*0101/DRB1*1101 （DR11）相关的表位的CD4(+) CTL。HCMV分离株的氨基酸序列比较表明，CD4(+) T细胞识别的gB和gH表位序列不仅在HCMV临床分离株中保守，而且在高等灵长类动物（黑猩猩、恒河猴和狒狒）的CMV分离株中也保守。有趣的是，这些来自黑猩猩、恒河猴和狒狒CMV的表位序列可以被人类CD4(+) CTL有效识别。更重要的是，我们发现来自人类的gb特异性T细胞也可以有效地裂解来自黑猩猩的肽致敏的Patr-DR7（+）细胞。这些发现提示在设计HCMV预防性疫苗时应考虑保守的gB和gH表位。此外，它们还为人类和旧大陆灵长类动物之间MHC 11类谱系的保存提供了功能基础，并为在HCMV疫苗开发中使用这种灵长类动物模型提供了可能性。
Although the importance of CD4(+) T cell responses to human cytonnegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4(+) CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HICMV isolates revealed that the gB and gH epitope sequences recognized by human CD4(+) T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4(+) CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse pepticle-sensitized Patr-DR7(+) cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class 11 lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.