Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and -A33.
Tumor-infiltrating lymphocytes (TILs) derived from tumor-bearing patients recognize tumor-associated Ags presented by MHC class I molecules. The infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Two T cell epitopes derived from tumor Ags, tyrosinase-related protein (TRP)-1 and TRP-2, were shown to be recognized by HLA-A31 restricted TIL586 and its T cell clones. In this study we tested the hypothesis that these two peptides can be recognized by CTL from non-HLA-A31 patients with melanoma. It was found that both peptides were capable of binding to HLA-A3, -A11, -A31, -A33, and -A68 of the HLA-A3 supertype. Importantly, we found that HLA-A33-positive TIL1244 and its T cell clones can recognize TRP197-205 presented by both HLA-A31 and -A33 molecules, suggesting that a single TCR can recognize peptide/A31 and peptide/A33 complexes. However, peptide titration experiments showed that the affinity of TCR receptor to peptide/A33 could be higher than that to the peptide/A31. These studies have important implications for the development of peptide-based cancer vaccines.
Wang
R F
RF
Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. rongfu@pop.nci.nih.gov
Johnston
S L
SL
Southwood
S
S
Sette
A
A
Rosenberg
S A
SA
D000951:Antigens, Neoplasm / Q000378:metabolism; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000276:immunology* / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000201:enzymology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C082945:HLA-A*33 antigen; C069527:HLA-A31 antigen; D010446:Peptide Fragments; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase