title: A Diverse Repertoire of CD4 T Cells Targets the Immediate-Early 1 Protein of Human Cytomegalovirus.
abstract: T-cell responses to the immediate-early 1 (IE-1) protein of human cytomegalovirus (HCMV) are associated with protection from viral disease. Thus, IE-1 is a promising target for immunotherapy. CD8 T-cell responses to IE-1 are generally strong. In contrast, CD4 T-cell responses to IE-1 were described to be comparatively infrequent or undetectable in HCMV carriers, and information on their target epitopes and their function has been limited. To analyze the repertoire of IE-1-specific CD4 T cells, we expanded them from healthy donors with autologous IE-1-expressing mini-Epstein-Barr virus-transformed B-cell lines and established IE-1-specific CD4 T-cell clones. Clones from seven out of seven HCMV-positive donors recognized endogenously processed IE-1 epitopes restricted through HLA-DR, DQ, or DP. Three to seven IE-1 epitopes were recognized per donor. Cumulatively, about 27 different HLA/peptide class II complexes were recognized by 117 IE-1-specific clones. Our results suggest that a highly diversified repertoire of IE-1-specific CD4 T cells targeting multiple epitopes is usually present in healthy HCMV carriers. Therefore, multiepitope approaches to immunomonitoring and immunotherapy will make optimal use of this potentially important class of HCMV-specific effector cells.
authors.affiliation: Clinical Cooperation Group Immunooncology, Helmholtz Zentrum München and Ludwig-Maximilians-Universität , Munich , Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ameres
authors.affiliation: Clinical Cooperation Group Immunooncology, Helmholtz Zentrum München and Ludwig-Maximilians-Universität , Munich , Germany ; Research Group Host Control of Viral Latency and Reactivation, Helmholtz Zentrum München , Munich , Germany ; German Research Center for Infection Research (DZIF) , Munich , Germany.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liang
authors.affiliation: Clinical Cooperation Group Immunooncology, Helmholtz Zentrum München and Ludwig-Maximilians-Universität , Munich , Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Wiesner
authors.affiliation: German Research Center for Infection Research (DZIF) , Munich , Germany ; Clinical Cooperation Group Pediatric Tumor Immunology, Helmholtz Zentrum München and Technische Universität München , Munich , Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Mautner
authors.affiliation: Clinical Cooperation Group Immunooncology, Helmholtz Zentrum München and Ludwig-Maximilians-Universität , Munich , Germany ; Research Group Host Control of Viral Latency and Reactivation, Helmholtz Zentrum München , Munich , Germany ; German Research Center for Infection Research (DZIF) , Munich , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Moosmann
keywords: CD4 T cells; CMV; HLA class II; IE-1; cytomegalovirus