Cross-presentation of HLA class I epitopes from exogenous NY-ESO-1 polypeptides by nonprofessional APCs.
NY-ESO-1, a germ cell Ag often detected in tumor tissues, frequently elicits Ab and CD8(+) T cell responses in cancer patients. Overlapping long peptides spanning the NY-ESO-1 sequence have been used to map HLA class I-restricted epitopes recognized by NY-ESO-1-specific CD8(+) T lymphocytes. To address the antigenicity of long peptides, we analyzed two synthetic 30-mer peptides from NY-ESO-1, polypeptides 80-109 and 145-174, for their capacity to be processed by APCs and to stimulate CD8(+) T cells. By incubating APCs with polypeptides at different temperatures or in the presence of protease inhibitors, we found that NY-ESO-1 polypeptides were rapidly internalized by B cells, T2 cells, or PBLs and submitted to cellular proteolytic action to yield nonamer epitopes presented by HLA class I. Polypeptides were also immunogenic in vitro and stimulated the expansion of CD8(+) T cells against naturally processed NY-ESO-1 epitopes in the context of three different HLA class I alleles. Polypeptides can thus serve as exogenous Ags that are cross-presented on HLA class I without requiring the action of professional APCs. These findings support innovative vaccination strategies using NY-ESO-1 polypeptides that would circumvent current limitations of HLA class I peptide vaccination, i.e., HLA eligibility criteria and knowledge of epitope, while allowing for facilitated immunogenicity in the presence of helper epitopes.
Gnjatic
Sacha
S
Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10021,USA. gnjatics@mskcc.org
Atanackovic
Djordje
D
Matsuo
Mitsutoshi
M
Jäger
Elke
E
Lee
Sang Yull
SY
Valmori
Danila
D
Chen
Yao-Tseng
YT
Ritter
Gerd
G
Knuth
Alexander
A
Old
Lloyd J
LJ
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D011506:Proteins / Q000276:immunology* / Q000378:metabolism*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D010446:Peptide Fragments; D011506:Proteins