Epitopes described in "Ex vivo IFN-gamma secretion by circulating CD8 T lymphocytes: implications of a novel approach for T cell monitoring in infectious and malignant diseases."

Article Authors:M J Pittet; A Zippelius; D E Speiser; M Assenmacher; P Guillaume; D Valmori; D LiƩnard; F Lejeune; J C Cerottini; P Romero
Article Title:Ex vivo IFN-gamma secretion by circulating CD8 T lymphocytes: implications of a novel approach for T cell monitoring in infectious and malignant diseases.
Reference Detail
Reference ID:315632
Abstract:To elucidate the functional heterogeneity of Ag-specific T lymphocyte populations, we combined labeling of lymphocytes with MHC/peptide tetramers and a cell surface affinity matrix for IFN-gamma. Magnetic cell sorting of IFN-gamma-positive lymphocytes allowed the selective enrichment and identification of live Ag-specific cytokine-secreting cells by flow cytometry. Naive, memory, and effector Ag-specific populations were evaluated in healthy HLA-A2 individuals. Significant fractions of influenza- and CMV-specific cells secreted IFN-gamma upon challenge with cognate peptide, consistent with an effector/memory status. The sensitivity of the approach allowed the detection of significant numbers of CMV-specific IFN-gamma-secreting cells ex vivo (i.e., without Ag stimulation). This was not apparent when using previously described assays, namely, ELISPOT or intracellular IFN-gamma staining (cytospot). CD8+ T cells specific for the melamoma-associated Ag Melan-A/MART-1 did not produce IFN-gamma upon challenge with cognate peptide, reminiscent with their naive functional state in healthy individuals. In contrast, CD45RA(low) Melan-A/MART-1 tumor-specific cells from three of three melanoma patients presented levels of activity similar to those found for influenza- or CMV virus-specific lymphocytes, compatible with a functional differentiation into competent effector/memory T lymphocytes in vivo. Notably, a sizable fraction of Melan-A/MART-1-specific cells from a patient secreted IFN-gamma ex vivo following peptide-based vaccination. Thus, the high sensitivity of the assay provides a valuable tool to monitor effector T cell responses in different clinical situations.
Affiliations:Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch, University Hospital, Lausanne, Switzerland.
Reference Type:Literature
PubMed ID:11390521
Journal:J Immunol
Journal Volume:166
Article Pages:7634-40
Journal ISSN:0022-1767
Article Chemical List:Antigens, Neoplasm;Epitopes, T-Lymphocyte;HLA-A2 Antigen;MART-1 Antigen;MLANA protein, human;Neoplasm Proteins;Peptide Fragments;Viral Matrix Proteins;influenza virus membrane protein (58-66);Interferon-gamma
Article MeSH List:Antigens, Neoplasm; CD8-Positive T-Lymphocytes(cytology; immunology; pathology; secretion); Cell Differentiation(immunology); Cytomegalovirus(immunology); Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte(analysis); Flow Cytometry; HLA-A2 Antigen(analysis; immunology); Humans; Immunomagnetic Separation; Immunophenotyping; Infant, Newborn; Influenza A virus(immunology); Interferon-gamma(blood; secretion); Lymphocyte Count; MART-1 Antigen; Melanoma(immunology; pathology; secretion); Monitoring, Immunologic(methods); Neoplasm Proteins(analysis; immunology); Peptide Fragments(analysis; immunology); Sensitivity and Specificity; Viral Matrix Proteins(analysis; immunology)
Article Comments:Data originally imported from the HLA Ligand Database (http://hlaligand.ouhsc.edu/)
Curation Last Updated:2014-10-03 19:45:40