Epitopes described in "Stimulation of human EBV- and CMV-specific cytolytic effector function using allogeneic HLA molecules."

Article Authors:Lloyd J D'Orsogna; Heleen van den Heuvel; Ellen M W van der Meer-Prins; Dave L Roelen; Ilias I N Doxiadis; Frans H J Claas
Article Title:Stimulation of human EBV- and CMV-specific cytolytic effector function using allogeneic HLA molecules.
Reference Detail
Reference ID:1025244
Abstract:Viral infection is a major cause of morbidity and mortality, and there are few therapeutic options available to augment a virus-specific T cell response. Although allo-HLA cross-reactivity from virus-specific memory T cells is common, it is unclear whether priming with specific allogeneic cells could conversely elicit a viral peptide/self-HLA restricted cytotoxic T cell response in humans. First, we used the previously described allo-HLA-B*44:02 cross-reactivity of EBV peptide/HLA-B8 restricted T cells, to determine whether allogeneic HLA stimulation can elicit a cytolytic immune response against EBV. HLA-B8(+) HLA-B44(-) EBV-seropositive PBMCs were stimulated with either HLA-B*44:02(+) or HLA-B*44:03(+) mismatched irradiated PBMCs in a 7-10 d MLR. The allo-HLA stimulated responder cells were then evaluated for cytotoxicity using EBV peptide loaded autologous target cells and unloaded HLA-B8(+) EBV LCL target cells. PBMCs from EBV-seropositive donors gained EBV-specific cytolytic effector function following specific allo-HLA stimulation. Finally, we also elicited cytolytic CMV-specific responses using specific allogeneic cell stimulation, to confirm that this technique can be used to elicit viral peptide/self-HLA restricted responses even from nonpublic TCR responses. Allogeneic cell stimulation used as a cell therapy may be a potential tool to augment an antiviral T cell response in patients with EBV or CMV infection.
Affiliations:Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden 2300 RC, The Netherlands. Lloyd.dorsogna@health.wa.gov.au
Reference Type:Literature
PubMed ID:23077240
Journal:J Immunol
Journal Volume:189
Article Pages:4825-31
Journal ISSN:0022-1767
Article Chemical List:HLA-B Antigens;Peptides;Viral Proteins
Article MeSH List:Cells, Cultured; Cytomegalovirus(immunology); Cytomegalovirus Infections(immunology); Epstein-Barr Virus Infections(immunology); Female; HLA-B Antigens(immunology); Herpesvirus 4, Human(immunology); Humans; Immunologic Memory; Male; Peptides(immunology); T-Lymphocytes, Cytotoxic(immunology); Viral Proteins(immunology)
Curation Last Updated:2014-11-19 20:42:15