title: Cross-presentation of HCMV chimeric protein enables generation and measurement of polyclonal T cells.
abstract: CD8(+) T cell immunity has a critical function in controlling human cytomegalovirus (HCMV) infection. In immunocompromized individuals, HCMV reactivation or disease can lead to increased morbidity and mortality, particularly in transplant recipients. In this setting, adoptive transfer of HCMV-specific CD8(+) T cells is a promising vaccine strategy to restore viral immunity, with most clinical approaches focussing on the use of peptides for the generation of single epitope-specific CD8(+) T cells. We show that using an IE1-pp65 chimeric protein as the antigen source promotes effective cross-presentation, by monocyte-derived dendritic cells (MoDCs), to generate polyclonal CD8(+) T cell epitopes. By exploring human leukocyte antigen (HLA)-restricted immunodominance hierarchies both within and across two immunodominant proteins, we show that HLA-B7 epitopes elicit higher CD8(+) T cell responses compared with HLA-A1, -A2 or -B8. This study provides important evidence highlighting both the efficacy of the IE1-pp65 chimeric protein and the importance of immunodominance in designing future therapeutic vaccines.
authors.affiliation: Malignant Haematology and Stem Cell Transplantation Service, The Alfred Hospital, Victoria, Australia.
authors.forename: Thi H O
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: Tom C
authors.initials: TC
authors.lastname: Kotsimbos
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mifsud
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045142:Cross-Priming; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000378:metabolism*; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D009000:Monocytes / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014775:Virus Activation
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; C464970:IE1-pp65 recombinant protein, Human cytomegalovirus; D017874:Immediate-Early Proteins; D016056:Immunodominant Epitopes; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins