TY - JOUR
T1 - Cytotoxic T cells directed to tumor antigens not expressed on normal melanocytes dominate HLA-A2.1-restricted immune repertoire to melanoma
AU - Anichini, Andrea
AU - Mortarini, Roberta
AU - Maccalli, Cristina
AU - Squarcina, Paola
AU - Fleischhauer, Katharina
AU - Mascheroni, Luigi
AU - Parmiani, Giorgio
PY - 1996/1/1
Y1 - 1996/1/1
N2 - To determine whether HLA-A2.1-restricted melanoma Ags exist that are not expressed on normal melanocytes, a panel of 478 T cell clones from six HLA- A2.1+ patients was selected for HLA-A2-restricted lysis of autologous tumor and then tested for differential recognition of HLA-A2.1+ melanomas and normal melanocytes. Four subsets of clones were identified in the panel of 107 HLA-A2-restricted CTL clones. CTL clones from three of the four subsets did not lyse melanocytes, but recognized fresh HLA-A2.1+ melanomas and defined three classes of epitopes, including unique Ags, common melanoma Ags, and Ags shared with neoplastic cells of different histologic origin. These CTL clones did not recognize any of the 10 peptides selected for specific association to HLA-A2.1 and derived from Melan-A/Mart-1, tyrosinase, gp100, or MAGE-3 proteins. By contrast, the fourth subset of HLA-A2.1-restricted CTL clones recognized both melanoma and melanocytes. These CTL clones were directed to a peptide from either Melan-A/Mart-1, tyrosinase, or gp100. By a limiting dilution assay, designed to evaluate the frequency of HLA-A2- restricted CTL precursors (CTLp) directed to melanoma but not to melanocytes, such precursors were found in the peripheral blood or tumor site of five of six HLA-A2.1+ melanoma patients, and their frequency was much higher than the frequency of CTLp recognizing both tumor cells and the melanocytes. These results suggest that in melanoma patients most of the HLA-A2.1-restricted immune repertoire to melanoma is directed to epitopes expressed in the neoplastic but not in the normal cells of the melanocyte lineage.
AB - To determine whether HLA-A2.1-restricted melanoma Ags exist that are not expressed on normal melanocytes, a panel of 478 T cell clones from six HLA- A2.1+ patients was selected for HLA-A2-restricted lysis of autologous tumor and then tested for differential recognition of HLA-A2.1+ melanomas and normal melanocytes. Four subsets of clones were identified in the panel of 107 HLA-A2-restricted CTL clones. CTL clones from three of the four subsets did not lyse melanocytes, but recognized fresh HLA-A2.1+ melanomas and defined three classes of epitopes, including unique Ags, common melanoma Ags, and Ags shared with neoplastic cells of different histologic origin. These CTL clones did not recognize any of the 10 peptides selected for specific association to HLA-A2.1 and derived from Melan-A/Mart-1, tyrosinase, gp100, or MAGE-3 proteins. By contrast, the fourth subset of HLA-A2.1-restricted CTL clones recognized both melanoma and melanocytes. These CTL clones were directed to a peptide from either Melan-A/Mart-1, tyrosinase, or gp100. By a limiting dilution assay, designed to evaluate the frequency of HLA-A2- restricted CTL precursors (CTLp) directed to melanoma but not to melanocytes, such precursors were found in the peripheral blood or tumor site of five of six HLA-A2.1+ melanoma patients, and their frequency was much higher than the frequency of CTLp recognizing both tumor cells and the melanocytes. These results suggest that in melanoma patients most of the HLA-A2.1-restricted immune repertoire to melanoma is directed to epitopes expressed in the neoplastic but not in the normal cells of the melanocyte lineage.
UR - http://www.scopus.com/inward/record.url?scp=0030029651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030029651&partnerID=8YFLogxK
M3 - Article
C2 - 8598464
AN - SCOPUS:0030029651
VL - 156
SP - 208
EP - 217
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -