HCMV triggers frequent and persistent UL40-specific unconventional HLA-E-restricted CD8 T-cell responses with potential autologous and allogeneic peptide recognition Article Swipe
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· 2018
· Open Access
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· DOI: https://doi.org/10.1371/journal.ppat.1007041
Immune response against human cytomegalovirus (HCMV) includes a set of persistent cytotoxic NK and CD8 T cells devoted to eliminate infected cells and to prevent reactivation. CD8 T cells against HCMV antigens (pp65, IE1) presented by HLA class-I molecules are well characterized and they associate with efficient virus control. HLA-E-restricted CD8 T cells targeting HCMV UL40 signal peptides (HLA-EUL40) have recently emerged as a non-conventional T-cell response also observed in some hosts. The occurrence, specificity and features of HLA-EUL40 CD8 T-cell responses remain mostly unknown. Here, we detected and quantified these responses in blood samples from healthy blood donors (n = 25) and kidney transplant recipients (n = 121) and we investigated the biological determinants involved in their occurrence. Longitudinal and phenotype ex vivo analyses were performed in comparison to HLA-A*02/pp65-specific CD8 T cells. Using a set of 11 HLA-E/UL40 peptide tetramers we demonstrated the presence of HLA-EUL40 CD8 αβT cells in up to 32% of seropositive HCMV+ hosts that may represent up to 38% of total circulating CD8 T-cells at a time point suggesting a strong expansion post-infection. Host's HLA-A*02 allele, HLA-E *01:01/*01:03 genotype and sequence of the UL40 peptide from the infecting strain are major factors affecting the incidence of HLA-EUL40 CD8 T cells. These cells are effector memory CD8 (CD45RAhighROlow, CCR7-, CD27-, CD28-) characterized by a low level of PD-1 expression. HLA-EUL40 responses appear early post-infection and display a broad, unbiased, Vβ repertoire. Although induced in HCMV strain-dependent, UL4015-23-specific manner, HLA-EUL40 CD8 T cells are reactive toward a broader set of nonapeptides varying in 1-3 residues including most HLA-I signal peptides. Thus, HCMV induces strong and life-long lasting HLA-EUL40 CD8 T cells with potential allogeneic or/and autologous reactivity that take place selectively in at least a third of infections according to virus strain and host HLA concordance.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.ppat.1007041
- https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007041&type=printable
- OA Status
- gold
- Cited By
- 37
- References
- 61
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2802657422
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2802657422Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.ppat.1007041Digital Object Identifier
- Title
-
HCMV triggers frequent and persistent UL40-specific unconventional HLA-E-restricted CD8 T-cell responses with potential autologous and allogeneic peptide recognitionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
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2018-04-30Full publication date if available
- Authors
-
Nicolas Jouand, Céline Bressollette‐Bodin, Nathalie Gérard, Magali Giral, Pierrick Guérif, Audrey Rodallec, Romain Oger, Tiphaine Parrot, Mathilde Allard, Anne Cesbron‐Gautier, Nadine Gervois, Béatrice CharreauList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.ppat.1007041Publisher landing page
- PDF URL
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https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007041&type=printableDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007041&type=printableDirect OA link when available
- Concepts
-
Cytotoxic T cell, CD8, Biology, Human leukocyte antigen, Immunology, T cell, CD28, Human cytomegalovirus, Antigen, Immune system, Virology, Virus, In vitro, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
37Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2024: 4, 2023: 6, 2022: 8, 2021: 6Per-year citation counts (last 5 years)
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61Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.control. | 48 |
| abstract_inverted_index.detected | 87 |
| abstract_inverted_index.effector | 209 |
| abstract_inverted_index.features | 76 |
| abstract_inverted_index.genotype | 184 |
| abstract_inverted_index.includes | 6 |
| abstract_inverted_index.infected | 20 |
| abstract_inverted_index.involved | 115 |
| abstract_inverted_index.observed | 68 |
| abstract_inverted_index.peptides | 57 |
| abstract_inverted_index.presence | 145 |
| abstract_inverted_index.reactive | 248 |
| abstract_inverted_index.recently | 60 |
| abstract_inverted_index.residues | 258 |
| abstract_inverted_index.response | 1, 66 |
| abstract_inverted_index.sequence | 186 |
| abstract_inverted_index.unknown. | 84 |
| abstract_inverted_index.HLA-EUL40 | 78, 147, 202, 224, 243, 271 |
| abstract_inverted_index.according | 292 |
| abstract_inverted_index.affecting | 198 |
| abstract_inverted_index.associate | 44 |
| abstract_inverted_index.cytotoxic | 11 |
| abstract_inverted_index.efficient | 46 |
| abstract_inverted_index.eliminate | 19 |
| abstract_inverted_index.expansion | 177 |
| abstract_inverted_index.incidence | 200 |
| abstract_inverted_index.including | 259 |
| abstract_inverted_index.infecting | 193 |
| abstract_inverted_index.life-long | 269 |
| abstract_inverted_index.molecules | 38 |
| abstract_inverted_index.peptides. | 263 |
| abstract_inverted_index.performed | 126 |
| abstract_inverted_index.phenotype | 121 |
| abstract_inverted_index.potential | 276 |
| abstract_inverted_index.presented | 34 |
| abstract_inverted_index.represent | 161 |
| abstract_inverted_index.responses | 81, 91, 225 |
| abstract_inverted_index.targeting | 53 |
| abstract_inverted_index.tetramers | 141 |
| abstract_inverted_index.unbiased, | 233 |
| abstract_inverted_index.HLA-E/UL40 | 139 |
| abstract_inverted_index.allogeneic | 277 |
| abstract_inverted_index.autologous | 279 |
| abstract_inverted_index.biological | 113 |
| abstract_inverted_index.comparison | 128 |
| abstract_inverted_index.infections | 291 |
| abstract_inverted_index.persistent | 10 |
| abstract_inverted_index.quantified | 89 |
| abstract_inverted_index.reactivity | 280 |
| abstract_inverted_index.recipients | 105 |
| abstract_inverted_index.suggesting | 174 |
| abstract_inverted_index.transplant | 104 |
| abstract_inverted_index.(HLA-EUL40) | 58 |
| abstract_inverted_index.circulating | 167 |
| abstract_inverted_index.expression. | 223 |
| abstract_inverted_index.occurrence, | 73 |
| abstract_inverted_index.occurrence. | 118 |
| abstract_inverted_index.repertoire. | 235 |
| abstract_inverted_index.selectively | 284 |
| abstract_inverted_index.specificity | 74 |
| abstract_inverted_index.Longitudinal | 119 |
| abstract_inverted_index.concordance. | 299 |
| abstract_inverted_index.demonstrated | 143 |
| abstract_inverted_index.determinants | 114 |
| abstract_inverted_index.investigated | 111 |
| abstract_inverted_index.nonapeptides | 254 |
| abstract_inverted_index.seropositive | 156 |
| abstract_inverted_index.*01:01/*01:03 | 183 |
| abstract_inverted_index.characterized | 41, 216 |
| abstract_inverted_index.reactivation. | 25 |
| abstract_inverted_index.post-infection | 228 |
| abstract_inverted_index.cytomegalovirus | 4 |
| abstract_inverted_index.post-infection. | 178 |
| abstract_inverted_index.HLA-E-restricted | 49 |
| abstract_inverted_index.non-conventional | 64 |
| abstract_inverted_index.(CD45RAhighROlow, | 212 |
| abstract_inverted_index.strain-dependent, | 240 |
| abstract_inverted_index.UL4015-23-specific | 241 |
| abstract_inverted_index.HLA-A*02/pp65-specific | 130 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 91 |
| corresponding_author_ids | https://openalex.org/A5062186392, https://openalex.org/A5062172662, https://openalex.org/A5089422245, https://openalex.org/A5047490177, https://openalex.org/A5046171847, https://openalex.org/A5084574852, https://openalex.org/A5057446768, https://openalex.org/A5031244376, https://openalex.org/A5112145344, https://openalex.org/A5016111785, https://openalex.org/A5082674992, https://openalex.org/A5049578005 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I154526488, https://openalex.org/I4210112643, https://openalex.org/I4210128919, https://openalex.org/I49451733, https://openalex.org/I97188460 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7699999809265137 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.91180831 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |