Naturally processed HLA-DR3-restricted HHV-6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T-cell responses
Authors
Becerra Artiles, AniuskaCruz, John
Leszyk, John D.
Sidney, John
Sette, Alessandro
Shaffer, Scott A.
Stern, Lawrence J.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyMass Spectrometry Facility
Department of Pathology
Document Type
Journal ArticlePublication Date
2019-08-01Keywords
CD4 T cellsHHV-6B
MHC-II-eluted peptides
cytotoxicity
polyfunctional response
UMCCTS funding
Amino Acids, Peptides, and Proteins
Cells
Enzymes and Coenzymes
Immunology and Infectious Disease
Translational Medical Research
Viruses
Metadata
Show full item recordAbstract
Human herpes virus 6B (HHV-6B) is a widespread virus that infects most people early in infancy and establishes a chronic life-long infection with periodic reactivation. CD4 T cells have been implicated in control of HHV-6B, but antigenic targets and functional characteristics of the CD4 T-cell response are poorly understood. We identified 25 naturally processed MHC-II peptides, derived from six different HHV-6B proteins, and showed that they were recognized by CD4 T-cell responses in HLA-matched donors. The peptides were identified by mass spectrometry after elution from HLA-DR molecules isolated from HHV-6B-infected T cells. The peptides showed strong binding to matched HLA alleles and elicited recall T-cell responses in vitro. T-cell lines expanded in vitro were used for functional characterization of the response. Responding cells were mainly CD3(+) CD4(+) , produced IFN-gamma, TNF-alpha, and low levels of IL-2, alone or in combination, highlighting the presence of polyfunctional T cells in the overall response. Many of the responding cells mobilized CD107a, stored granzyme B, and mediated specific killing of peptide-pulsed target cells. These results highlight a potential role for polyfunctional cytotoxic CD4 T cells in the long-term control of HHV-6B infection.Source
Becerra-Artiles A, Cruz J, Leszyk JD, Sidney J, Sette A, Shaffer SA, Stern LJ. Naturally processed HLA-DR3-restricted HHV-6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T-cell responses. Eur J Immunol. 2019 Aug;49(8):1167-1185. doi: 10.1002/eji.201948126. Epub 2019 May 2. PMID: 31020640. Link to article on publisher's site
DOI
10.1002/eji.201948126Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50374PubMed ID
31020640Related Resources
ae974a485f413a2113503eed53cd6c53
10.1002/eji.201948126