CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.
We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1. In the present study, we have analyzed in detail the relative antigenicity and in vitro immunogenicity of natural and modified NY-ESO-1 peptide sequences. The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients. In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently. In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level. Among natural peptides, NY-ESO-1 157-165 and NY-ESO-1 157-167 exhibited good in vitro immunogenicity, whereas peptide NY-ESO-1 155-163 was poorly immunogenic. The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions. The findings reported here have significant implications for the formulation of NY-ESO-1-based vaccines as well as for the monitoring of either natural or vaccine-induced NY-ESO-1-specific CTL responses in cancer patients.
Romero
P
P
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch, Centre Hospitalier Universitaire Vaudois, Switzerland.
Dutoit
V
V
Rubio-Godoy
V
V
Liénard
D
D
Speiser
D
D
Guillaume
P
P
Servis
K
K
Rimoldi
D
D
Cerottini
J C
JC
Valmori
D
D
D000941:Antigens / Q000378:metabolism*; D000951:Antigens, Neoplasm; D001667:Binding, Competitive; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000941:Antigens; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D010455:Peptides; D011506:Proteins; D007371:Interferon-gamma