Antigen-Specific TCR Signatures of Cytomegalovirus Infection.
J Immunol
; 202(3): 979-990, 2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30587531
ABSTRACT
CMV is a prevalent human pathogen. The virus cannot be eliminated from the body, but is kept in check by CMV-specific T cells. Patients with an insufficient T cell response, such as transplant recipients, are at high risk of developing CMV disease. However, the CMV-specific T cell repertoire is complex, and it is not yet clear which T cells protect best against virus reactivation and disease. In this study, we present a highly resolved characterization of CMV-specific human CD8+ T cells based on enrichment by specific peptide stimulation and mRNA sequencing of their TCR ß-chains (TCRß). Our analysis included recently identified T cell epitopes restricted through HLA-C, whose presentation is resistant to viral immunomodulation, and well-studied HLA-B-restricted epitopes. In eight healthy virus carriers, we identified a total of 1052 CMV-specific TCRß sequences. HLA-C-restricted, CMV-specific TCRß clonotypes dominated the ex vivo T cell response and contributed the highest-frequency clonotype of the entire repertoire in two of eight donors. We analyzed sharing and similarity of CMV-specific TCRß sequences and identified 63 public or related sequences belonging to 17 public TCRß families. In our cohort, and in an independent cohort of 352 donors, the cumulative frequency of these public TCRß family members was a highly discriminatory indicator of carrying both CMV infection and the relevant HLA type. Based on these findings, we propose CMV-specific TCRß signatures as a biomarker for an antiviral T cell response to identify patients in need of treatment and to guide future development of immunotherapy.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T alfa-beta
/
Infecções por Citomegalovirus
/
Epitopos de Linfócito T
/
Antígenos Virais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha