A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells.
A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells.
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病毒CTL逃逸突变导致免疫球蛋白样转录本4介导的骨髓细胞细胞的功能抑制。
DOI：
10.1084/jem.20061865
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发表时间：
2007-11-26
影响因子：
15.3
通讯作者：
Yu, Xu G.
中科院分区：
文献类型：
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作者：
Lichterfeld, Mathias;Kavanagh, Daniel G.;Williams, Katie L.;Moza, Beenu;Mui, Stanley K.;Miura, Toshiyuki;Sivamurthy, Rohini;Allgaier, Rachel;Pereyra, Florencia;Trocha, Alicja;Feeney, Margaret;Gandhi, Rajesh T.;Rosenberg, Eric S.;Altfeld, Marcus;Allen, Todd M.;Allen, Rachel;Walker, Bruce D.;Sundberg, Eric J.;Yu, Xu G.
病毒突变逃逸可以减少或消除病毒特异性CD 8 + T细胞的T细胞受体（TCR）的识别。然而，很少有人知道的影响细胞毒性T淋巴细胞（CTL）表位突变的肽-主要组织相容性复合物（MHC）I类复合物和MHC I类受体表达的其他细胞类型之间的相互作用。在这里，我们分析了免疫显性人类白细胞抗原（HLA）-B2705限制性HIV-1 Gag KK 10表位的变体（KRWIILGLNK），其在位置6（L 6 M）处具有L至M氨基酸取代，其在初次感染后作为CTL逃逸变体产生，但具有足够的免疫原性以引发二次，慢性感染中具有替代TCR库的从头HIV-1特异性CD 8 + T细胞应答。除了改变HIV-1特异性CD 8 + T细胞的识别外，HLA-B2705-KK 10 L 6 M复合物还表现出与免疫球蛋白样转录物（ILT）受体4（一种在骨髓单核细胞上表达的抑制性MHC I类特异性受体）的结合显著增加。B2705-KK 10 L 6 M复合物与ILT 4的结合导致骨髓单核细胞的致耐受性表型，其具有树突状细胞（DC）成熟标志物和共刺激分子的较低表面表达。这些数据表明，CTL驱动的突变逃逸，改变识别先天性MHC I类受体的骨髓单核细胞，和功能障碍的DC之间的联系，从而提供了重要的新的洞察病毒序列多样化的生物学后果。
Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversification.
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HIV-1 GAG中的簇突变是逃避HLA-B27限制的细胞毒性T淋巴细胞反应所必需的。
影响因子：
15.3
作者：
Kelleher, A D;Long, C;Holmes, E C;Allen, R L;Wilson, J;Conlon, C;Workman, C;Shaunak, S;Olson, K;Goulder, P;Brander, C;Ogg, G;Sullivan, J S;Dyer, W;Jones, I;McMichael, A J;Rowland-Jones, S;Phillips, R E
通讯作者：
Phillips, R E
影响因子：
64.8
作者：
Goulder, PJR;Brander, C;Walker, BD
通讯作者：
Walker, BD
影响因子：
5.4
作者：
Allen, TM;Altfeld, M;Walker, BD
通讯作者：
Walker, BD
DOI：
10.1084/jem.186.11.1809
发表时间：
1997-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Colonna M;Navarro F;Bellón T;Llano M;García P;Samaridis J;Angman L;Cella M;López-Botet M
通讯作者：
López-Botet M
影响因子：
2.9
作者：
Lefranc, MP;Pommié, C;Lefranc, G
通讯作者：
Lefranc, G