Title

Naturally processed HLA-DR3-restricted HHV-6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T-cell responses

UMMS Affiliation

Department of Pathology; Mass Spectrometry Facility; Department of Biochemistry and Molecular Pharmacology

Publication Date

2019-04-25

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cells | Enzymes and Coenzymes | Immunology and Infectious Disease | Translational Medical Research | Viruses

Abstract

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.

Keywords

CD4 T cells, HHV-6B, MHC-II-eluted peptides, cytotoxicity, polyfunctional response, UMCCTS funding

DOI of Published Version

10.1002/eji.201948126

Source

Eur J Immunol. 2019 Apr 25. doi: 10.1002/eji.201948126. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

European journal of immunology

Related Resources

Link to Article in PubMed

PubMed ID

31020640

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