Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele

Sacha Gnjatic, Yasuhiro Nagata, Elke Jäger, Elisabeth Stockert, Srinivas Shankara, Bruce L. Roberts, Gail P. Mazzara, Sang Yull Lee, P. Rod Dunbar, Bo Dupont, Vincenzo Cerundolo, Gerd Ritter, Yao Tseng Chen, Alexander Knuth, Lloyd J. Old

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

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.

Original languageEnglish
Pages (from-to)10917-10922
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number20
DOIs
StatePublished - 26 Sep 2000
Externally publishedYes

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