期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 49, 期 8, 页码 1167-1185出版社
WILEY
DOI: 10.1002/eji.201948126
关键词
CD4 T cells; cytotoxicity; HHV-6B; MHC-II-eluted peptides; polyfunctional response
类别
资金
- NIH [U19-AI109858, HHSN272201400046C, HHSN272201400045C]
- National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health [UL1-TR001453]
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.
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