Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele.
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-1 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.
Gnjatic
S
S
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. s-gnjatic@ski.mskcc.org
Nagata
Y
Y
Jager
E
E
Stockert
E
E
Shankara
S
S
Roberts
B L
BL
Mazzara
G P
GP
Lee
S Y
SY
Dunbar
P R
PR
Dupont
B
B
Cerundolo
V
V
Ritter
G
G
Chen
Y T
YT
Knuth
A
A
Old
L J
LJ
D000483:Alleles; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011506:Proteins