Cytomegalovirus-Specific T Cell Epitope Recognition in Congenital Cytomegalovirus Mother-Infant Pairs
Authors
Materne, Emma C.Lilleri, Daniele
Garofoli, Francesca
Lombardi, Giuseppina
Furione, Milena
Zavattoni, Maurizio
Gibson, Laura L.
UMass Chan Affiliations
Department of Pediatrics, Division of Pediatric Immunology and Infectious DiseasesDepartment of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2020-11-24Keywords
T cellcongenital infection
cytomegalovirus
epitope
immune escape
immunology
mother-infant pairs
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Immunology of Infectious Disease
Infectious Disease
Virus Diseases
Viruses
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Show full item recordAbstract
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-gamma 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.Source
Materne EC, Lilleri D, Garofoli F, Lombardi G, Furione M, Zavattoni M, Gibson L. Cytomegalovirus-Specific T Cell Epitope Recognition in Congenital Cytomegalovirus Mother-Infant Pairs. Front Immunol. 2020 Nov 24;11:568217. doi: 10.3389/fimmu.2020.568217. PMID: 33329532; PMCID: PMC7732427. Link to article on publisher's site
DOI
10.3389/fimmu.2020.568217Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41666PubMed ID
33329532Related Resources
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Copyright © 2020 Materne, Lilleri, Garofoli, Lombardi, Furione, Zavattoni and Gibson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2020.568217
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Except where otherwise noted, this item's license is described as Copyright © 2020 Materne, Lilleri, Garofoli, Lombardi, Furione, Zavattoni and Gibson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.