Cytomegalovirus-Specific T Cell Epitope Recognition in Congenital Cytomegalovirus Mother-Infant Pairs.
Cytomegalovirus-Specific T Cell Epitope Recognition in Congenital Cytomegalovirus Mother-Infant Pairs.
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DOI：
10.3389/fimmu.2020.568217
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发表时间：
2020
影响因子：
7.3
通讯作者：
Gibson L
中科院分区：
文献类型：
--
作者：
Materne EC;Lilleri D;Garofoli F;Lombardi G;Furione M;Zavattoni M;Gibson L
背景：先天性巨细胞病毒（cCMV）感染是出生前获得的最常见的感染，大约20%的婴儿在出生时无论是否有症状，都会出现永久性的神经发育影响。病毒逃离宿主免疫控制可能是CMV传播和婴儿疾病严重程度的机制之一。我们试图鉴定和比较母婴对识别的巨细胞病毒表位。我们还假设，如果免疫逃逸发生，那么受共享HLA等位基因限制的纵向CD8 T细胞反应的一种模式将是母体（通过病毒逃逸）失去CMV表位识别，而婴儿（通过病毒还原为野生型）获得CMV表位识别。方法：研究人群包括6例妊娠期原发性巨细胞病毒感染的妇女及其感染巨细胞病毒的婴儿。鉴定出已知或预测受母体MHC I类等位基因限制的CMV UL83和UL123肽，并根据几个标准选择一个子集进行检测。在IFN-γ ELISpot检测中，用巨细胞病毒肽刺激母细胞或婴儿细胞。结果：总体而言，母亲-婴儿对识别的25个肽中有14个（56%；8个UL83和6个UL123）未被报道为CD8 T细胞表位。在三对纵向样本中，一对显示母亲对CMV表位的损失和婴儿对共享HLA等位基因限制的CMV表位的增加。结论：CD8 T细胞对多种新的巨细胞病毒表位有应答，特别是在婴儿中。此外，在一对母婴中观察到CMV免疫逃逸的假设模式。这些发现强调，配对CMV表位识别的知识允许探索可能在母胎系统中运作的病毒免疫逃逸。我们的工作为进一步研究CMV在妊娠期传播的潜在机制或cCMV感染婴儿的临床结果提供了理论基础。
Background: Congenital cytomegalovirus (cCMV) infection is the most common infection acquired before birth and from which about 20% of infants develop permanent neurodevelopmental effects regardless of presence or absence of symptoms at birth. Viral escape from host immune control may be a mechanism of CMV transmission and infant disease severity. We sought to identify and compare CMV epitopes recognized by mother-infant pairs. We also hypothesized that if immune escape were occurring, then one pattern of longitudinal CD8 T cell responses restricted by shared HLA alleles would be maternal loss (by viral escape) and infant gain (by viral reversion to wildtype) of CMV epitope recognition. Methods: The study population consisted of 6 women with primary CMV infection during pregnancy and their infants with cCMV infection. CMV UL83 and UL123 peptides with known or predicted restriction by maternal MHC class I alleles were identified, and a subset was selected for testing based on several criteria. Maternal or infant cells were stimulated with CMV peptides in the IFN-γ ELISpot assay. Results: Overall, 14 of 25 (56%; 8 UL83 and 6 UL123) peptides recognized by mother-infant pairs were not previously reported as CD8 T cell epitopes. Of three pairs with longitudinal samples, one showed maternal loss and infant gain of responses to a CMV epitope restricted by a shared HLA allele. Conclusions: CD8 T cell responses to multiple novel CMV epitopes were identified, particularly in infants. Moreover, the hypothesized pattern of CMV immune escape was observed in one mother-infant pair. These findings emphasize that knowledge of paired CMV epitope recognition allows exploration of viral immune escape that may operate within the maternal-fetal system. Our work provides rationale for future studies of this potential mechanism of CMV transmission during pregnancy or clinical outcomes of infants with cCMV infection.
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影响因子：
6.4
作者：
Du Y;Zhang TH;Dai L;Zheng X;Gorin AM;Oishi J;Wu TT;Yoshizawa JM;Li X;Yang OO;Martinez-Maza O;Detels R;Sun R
通讯作者：
Sun R
影响因子：
9.1
作者：
Gibson, Laura;Barysauskas, Constance M.;McManus, Margaret;Dooley, Sheryl;Lilleri, Daniele;Fisher, Donna;Srivastava, Tumul;Diamond, Don J.;Luzuriaga, Katherine
通讯作者：
Luzuriaga, Katherine
影响因子：
15.9
作者：
Liu, Michael K. P.;Hawkins, Natalie;Goonetilleke, Nilu
通讯作者：
Goonetilleke, Nilu
影响因子：
2.2
作者：
Jones, N;Agrawal, D;Cao, HY
通讯作者：
Cao, HY
影响因子：
6.4
作者：
Lilleri, Daniele;Fornara, Chiara;Gerna, Giuseppe
通讯作者：
Gerna, Giuseppe