Epitopes described in "A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy."

Article Authors:Aisha N Hasan; Wouter J Kollen; Deepa Trivedi; Annamalai Selvakumar; Bo Dupont; Michel Sadelain; Richard J O'Reilly
Article Title:A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy.
Reference Detail
Reference ID:1016518
Abstract:Adoptive transfer of virus-specific T cells can treat infections complicating allogeneic hematopoietic cell transplants. However, autologous APCs are often limited in supply. In this study, we describe a panel of artificial APCs (AAPCs) consisting of murine 3T3 cells transduced to express human B7.1, ICAM-1, and LFA-3 that each stably express one of a series of six common HLA class I alleles. In comparative analyses, T cells sensitized with AAPCs expressing a shared HLA allele or autologous APCs loaded with a pool of 15-mer spanning the sequence of CMVpp65 produced similar yields of HLA-restricted CMVpp65-specific T cells; significantly higher yields could be achieved by sensitization with AAPCs transduced to express the CMVpp65 protein. T cells generated were CD8(+), IFN-gamma(+), and exhibited HLA-restricted CMVpp65-specific cytotoxicity. T cells sensitized with either peptide-loaded or transduced AAPCs recognized epitopes presented by each HLA allele known to be immunogenic in humans. Sensitization with AAPCs also permitted expansion of IFN-gamma(+) cytotoxic effector cells against subdominant epitopes that were either absent or in low frequencies in T cells sensitized with autologous APCs. This replenishable panel of AAPCs can be used for immediate sensitization and expansion of virus-specific T cells of desired HLA restriction for adoptive immunotherapy. It may be of particular value for recipients of transplants from HLA-disparate donors.
Affiliations:Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Reference Type:Literature
PubMed ID:19635907
Journal:J Immunol
Journal Volume:183
Article Pages:2837-50
Journal ISSN:0022-1767
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2cd5543e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@698dc970;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5ba40e33;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6fa06545;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@b58ce44;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@734dd82d;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@7babad7e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@440b6aa0;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@49855146;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4f9af05f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@451b15cd;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@7534692c;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@43e503d1;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@705db129;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@171a3461;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@3964d820;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@ba93a50;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@1333602b
Article MeSH List:Alleles; Animals; Cells, Cultured; Cytomegalovirus(immunology); Epitopes, T-Lymphocyte(immunology); HLA-A Antigens(genetics); HLA-A2 Antigen; HLA-A24 Antigen; HLA-A3 Antigen; HLA-B Antigens(genetics); HLA-B7 Antigen; HLA-B8 Antigen; Histocompatibility Antigens Class I(biosynthesis; genetics); Humans; Immunodominant Epitopes(administration & dosage; immunology); Immunotherapy, Adoptive; Lymphocyte Activation(immunology); Mice; NIH 3T3 Cells; Phosphoproteins(administration & dosage; immunology); T-Lymphocyte Subsets(immunology; transplantation; virology); T-Lymphocytes, Cytotoxic(immunology; transplantation; virology); Viral Matrix Proteins(administration & dosage; immunology)
Curation Last Updated:2015-01-17 22:33:07