Epitopes described in "Generation of CMV-specific T lymphocytes using protein-spanning pools of pp65-derived overlapping pentadecapeptides for adoptive immunotherapy."

Article Authors:Deepa Trivedi; Roxanne Y Williams; Richard J O'Reilly; Guenther Koehne
Article Title:Generation of CMV-specific T lymphocytes using protein-spanning pools of pp65-derived overlapping pentadecapeptides for adoptive immunotherapy.
Reference Detail
Reference ID:618
Abstract:Cell-mediated immunity is essential for control of human cytomegalovirus (HCMV) infection. We used a pool of 138 synthetic overlapping pentadecapeptides overspanning the entire pp65 protein to generate polyclonal CMV-specific T-cell lines from 12 CMV-seropositive donors inheriting different HLA genotypes. Autologous monocyte-derived dendritic cells (DCs) pulsed with this complete pool consistently induced highly specific T cells that selectively recognized 1-3 pentadecapeptides identified by secondary responses to a mapping grid of pentadecapeptide subpools with single overlaps. Responses against peptide-loaded targets sharing single HLA class I or II alleles identified the restricting HLA alleles. HLA-A*0201+ donors consistently responded to pentadecapeptides containing HLA-A*0201-binding epitope(aa495-503)NLVPMVATV. T-cell lines from other donors contained high frequencies of CD4 and/or CD8 T cells selectively reactive against peptides presented by other HLA alleles, including both known epitopes such as (aa341-350)QYDPVAALF (HLA-A*2402) as well as unreported epitopes such as (aa267-275)HERNGFTVL (HLA-B*4001 and B*4002) and (aa513-523)FFWDANDIYRI (HLA-DRB1*1301). These T cells consistently lysed CMV-infected target cells. Thus, this approach fosters expansion and selection of HLA-restricted CMV-pp65-reactive T-cell lines of high specificity that also lyse CMV-infected targets, and from a functional and regulatory perspective, may have advantages for generating virus-specific T cells for adoptive immunotherapy.
Affiliations:Allogenic Bone Marrow Transplantation Service, Department of Pediatrics, Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Reference Type:Literature
PubMed ID:15514011
Journal Volume:105
Article Pages:2793-801
Journal ISSN:0006-4971
Article Chemical List:Epitopes, T-Lymphocyte;Histocompatibility Antigens Class II;Phosphoproteins;Viral Matrix Proteins;cytomegalovirus matrix protein 65kDa
Article MeSH List:Amino Acid Sequence; CD4-Positive T-Lymphocytes(immunology; virology); Cell Line; Cytomegalovirus Infections(immunology; therapy); Epitopes, T-Lymphocyte(immunology); Fibroblasts(cytology); Genotype; Histocompatibility Antigens Class II(genetics; immunology); Humans; Immunotherapy, Adoptive(methods); In Vitro Techniques; Molecular Sequence Data; Phosphoproteins(genetics; immunology); Viral Matrix Proteins(genetics; immunology)
Curation Last Updated:2015-06-05 00:10:56