A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected Thais.
A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected Thais.
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DOI：
10.1371/journal.pone.0023603
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ruxrungtham K
中科院分区：
文献类型：
--
作者：
Buranapraditkun S;Hempel U;Pitakpolrat P;Allgaier RL;Thantivorasit P;Lorenzen SI;Sirivichayakul S;Hildebrand WH;Altfeld M;Brander C;Walker BD;Phanuphak P;Hansasuta P;Rowland-Jones SL;Allen TM;Ruxrungtham K
CD 8 + T细胞应答在HIV-1的控制中起重要作用。HIV-1广泛的序列多样性是开发有效HIV-1疫苗的关键障碍，可能需要区域特异性疫苗株来克服分布在世界各地的不同HIV-1进化枝的多样性。不幸的是，对CRF01_AE的CD 8 + T细胞应答知之甚少，这是东南亚大多数感染的原因。为了鉴定在HIV-1进化枝CRF01_AE感染的受试者中识别的显性CD 8 + T细胞应答，我们利用来自100名HIV-1进化枝CRF01_AE感染的受试者的免疫学筛选的数据，使用IFN-γ ELISpot来表征HLA-Cw*0102限制的HIV-1 Gag中的新型免疫显性CD 8 + T细胞应答（p24，277 YSPVSILDI 285，YI 9）。超过75%的Cw*0102+ve受试者靶向该表位，这代表了这些个体中超过三分之一的最强应答。这种新的CD 8表位位于HIV-1 Gag的高度保守区域，已知该区域含有免疫显性CD 8表位，其在进化枝B感染中受到HLA-B *57和-B*27的限制。尽管如此，在Cw*0102+ve受试者中经常观察到该表位中的病毒逃逸，表明这种常见的CD 8 + T细胞应答施加了强大的选择压力。由于HLA-Cw*0102在泰国人群中频繁表达（等位基因频率为16.8%），这种免疫显性Cw*0102限制性Gag表位可能代表了CRF01_AE特异性疫苗的有吸引力的候选者，并可能有助于进一步研究这种未充分研究的HIV-1进化枝的免疫发病机制。
CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia. To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, 277YSPVSILDI285, YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response. As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade.
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影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
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Robertson, Michael N.
影响因子：
32.4
作者：
Cohen, GB;Gandhi, RT;Baltimore, D
通讯作者：
Baltimore, D
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3.8
作者：
Hemelaar, Joris;Gouws, Eleanor;Osmanov, Saladin
通讯作者：
Osmanov, Saladin
影响因子：
82.9
作者：
Goulder, PJR;Phillips, RE;RowlandJones, S
通讯作者：
RowlandJones, S
影响因子：
82.9
作者：
Kaslow, RA;Carrington, M;Mann, DL
通讯作者：
Mann, DL