Naturally processed HLA-DR3-restricted HHV-6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T-cell responses
Department of Pathology; Mass Spectrometry Facility; Department of Biochemistry and Molecular Pharmacology
Amino Acids, Peptides, and Proteins | Cells | Enzymes and Coenzymes | Immunology and Infectious Disease | Translational Medical Research | Viruses
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.
CD4 T cells, HHV-6B, MHC-II-eluted peptides, cytotoxicity, polyfunctional response, UMCCTS funding
DOI of Published Version
Eur J Immunol. 2019 Apr 25. doi: 10.1002/eji.201948126. [Epub ahead of print] Link to article on publisher's site
European journal of immunology
Becerra Artiles, Aniuska; Cruz, John; Leszyk, John D.; Sidney, John; Sette, Alessandro; Shaffer, Scott A.; and Stern, Lawrence J., "Naturally processed HLA-DR3-restricted HHV-6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T-cell responses" (2019). UMass Center for Clinical and Translational Science Supported Publications. 201.