Authors: | Gnjatic, S.; Nagata, Y.; Jäger, E.; Stockert, E.; Shankara, S.; Roberts, B. L.; Mazzara, G. P.; Lee, S. Y.; Dunbar, P. R.; Dupont, B.; Cerundolo, V.; Ritter, G.; Chen, Y. T.; Knuth, A.; Old, L. J. |
Article Title: | Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele |
Abstract: | NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by strong CD8+ T cell responses against HLA-A2-restricted epitopes. To broaden the range of cancer patients who can be assessed for immunity to NY-ESO-1, a general method was devised to detect T cell reactivity independent of prior characterization of epitopes. A recombinant adenoviral vector encoding the full cDNA sequence of NY-ESO-I was used to transduce CD8-depleted peripheral blood lymphocytes as antigen-presenting cells. These modified antigen-presenting cells were then used to restimulate memory effector cells against NY-ESO-1 from the peripheral blood of cancer patients. Specific CD8+ T cells thus sensitized were assayed on autologous B cell targets infected with a recombinant vaccinia virus encoding NY-ESO-1. Strong polyclonal responses were observed against NY-ESO-1 in antibody-positive patients, regardless of their HLA profile. Because the vectors do not cross-react immunologically, only responses to NY-ESO-1 were detected. The approach described here allows monitoring of CD8+ T cell responses to NY-ESO-1 in the context of various HLA alleles and has led to the definition of NY-ESO-1 peptides presented by HLA-Cw3 and HLA-Cw6 molecules. |
Keywords: | human cell; cd8 antigen; cd8-positive t-lymphocytes; proteins; allele; alleles; cancer cell culture; genetic vectors; oncogene; antigen presentation; antigens, neoplasm; epitope; hla antigen class 1; histocompatibility antigens class i; melanoma cell; vaccinia virus; cytotoxicity, immunologic; diagnostic test; t lymphocyte activation; complementary dna; peripheral lymphocyte; gene transfer techniques; polyclonal activation; cancer; human; priority journal; article; support, u.s. gov't, p.h.s.; oncogene ny eso 1 |
Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
Volume: | 97 |
Issue: | 20 |
ISSN: | 0027-8424 |
Publisher: | National Academy of Sciences |
Date Published: | 2000-09-26 |
Start Page: | 10917 |
End Page: | 10922 |
Language: | English |
PUBMED: | 11005863 |
PROVIDER: | scopus |
PMCID: | PMC27124 |
DOI: | 10.1073/pnas.97.20.10917 |
DOI/URL: | |
Notes: | Export Date: 18 November 2015 -- Source: Scopus |