Novel HLA-Cw8-restricted T cell epitopes derived from tyrosinase-related protein-2 and gp100 melanoma antigens.
The identification of T cell epitopes presented by alternative HLA-B and -C alleles may provide a means to counteract the tumor escape mechanism based on the selection of tumor cells no longer susceptible to HLA-A-restricted T cell recognition. Several T cell clones and lines were obtained from T lymphocytes purified from melanoma-infiltrated or noninfiltrated lymph nodes of a patient who remained disease free 8 yr after surgery. Selected T cells recognized the autologous melanoma as evaluated by direct cytolysis and production of cytokines. These effectors were directed against the tyrosinase-related protein-2 (TRP-2) and gp100 melanoma epitopes restricted by HLA-Cw8. The nonamer and decamer peptides containing the sequence ANDPIFVVL (residues 387-395) of TRP-2 and the octamer, nonamer, and decamer peptides containing the sequence SNDGPTLI (residues 71-78) of gp100 reconstituted the epitope for TRP-2- and gp100-specific T cell lines and clones, respectively. However, only the nonameric form of TRP-2 and the nonameric and octameric forms of gp100 were able to induce peptide-specific T cells recognizing the autologous tumor in an HLA-class I-restricted fashion from PBMC of the melanoma patient studied. Together these data indicate that HLA-Cw8 can restrict the recognition of gp100 and TRP-2 epitopes by CTL, and that such peptides could stimulate a patient's PBL, suggesting that these Ags could have contributed to a systemic immunity against melanoma.
Castelli
C
C
Division of Experimental Oncology D, Istituto Nazionale Tunori, Milan, Italy. Castelli@istitutotumori.mi.it
Tarsini
P
P
Mazzocchi
A
A
Rini
F
F
Rivoltini
L
L
Ravagnani
F
F
Gallino
F
F
Belli
F
F
Parmiani
G
G
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000235:genetics; D019556:COS Cells; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D059909:HLA-B14 Antigen; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D019746:Intramolecular Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen