TY - JOUR
T1 - Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and -A33
AU - Wang, Rongfu
AU - Johnston, Samuel L.
AU - Southwood, Scott
AU - Sette, Alessandro
AU - Rosenberg, Steven A.
PY - 1998/1/15
Y1 - 1998/1/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9551926
AN - SCOPUS:0031974725
VL - 160
SP - 890
EP - 897
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -