Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pediatrics, Division of Pediatric Immunology and Infectious Diseases
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Immunology of Infectious Disease | Infectious Disease | Virus Diseases | Viruses
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.
T cell, congenital infection, cytomegalovirus, epitope, immune escape, immunology, mother-infant pairs
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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.
DOI of Published Version
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
Frontiers in immunology
Materne EC, Lilleri D, Garofoli F, Lombardi G, Furione M, Zavattoni M, Gibson LL. (2020). Cytomegalovirus-Specific T Cell Epitope Recognition in Congenital Cytomegalovirus Mother-Infant Pairs. Open Access Publications by UMMS Authors. https://doi.org/10.3389/fimmu.2020.568217. Retrieved from https://escholarship.umassmed.edu/oapubs/4458
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