TY - JOUR
T1 - Multiple Melanoma-Associated Epitopes Recognized by HLA-A3-Restricted CTLs and Shared by Melanomas but Not Melanocytes
AU - Mazzocchi, Arabella
AU - Storkus, Walter J.
AU - Traversari, Catia
AU - Tarsini, Paolo
AU - Maeurer, Markus J.
AU - Rivoltini, Licia
AU - Vegetti, Claudia
AU - Belli, Filiberto
AU - Anichini, Andrea
AU - Parmiani, Giorgio
AU - Castelli, Chiara
PY - 1996/10/1
Y1 - 1996/10/1
N2 - The molecular characterization of melanoma-associated Ags allowed the definition of several HLA class I-presented peptides recognized by T cells. However, no HLA-A3.1-restricted melanoma epitopes have been identified to date. To gain insight into the HLA-A3.1-restricted T cell epitope repertoire of human melanoma, we analyzed the immunologic reactivity of CTLs isolated from tumor-involved or tumor-free lymph nodes in two HLA-A3.1+ melanoma patients. Three CTL lines, clonal or highly oligoclonal in their TCR composition, and two CTL clones were selected for HLA class I-restricted lysis of the autologous tumor and then tested for the recognition of HLA-A3+ and HLA-A3- normal or neoplastic cells of the melanocyte lineage. One CTL recognized a unique HLA-A3.1-restricted Ag expressed only by the autologous tumors, while all the other CTLs defined three HLA-A3.1 epitopes shared by melanomas, but not by melanocytes. Moreover, the epitopes of two CTL lines with different specificity were reconstituted by nonoverlapping fractions of HLA-A3+ melanoma-derived peptides resolved by reverse phase-HPLC, indicating that distinct naturally processed peptides were specifically recognized on melanoma cells in association with HLA-A3.1 molecules. These novel lineage-unrelated HLA-A3.1-restricted melanoma epitopes do not derive from MAGE, BAGE, or GAGE gene families, as evaluated by the COS-7 transfection assay. Our data show that CTLs may recognize HLA-A3.1-class I complexes presenting melanoma (but not melanocyte)-associated epitopes that are either unique to a given patient's tumor or that are shared between multiple melanomas.
AB - The molecular characterization of melanoma-associated Ags allowed the definition of several HLA class I-presented peptides recognized by T cells. However, no HLA-A3.1-restricted melanoma epitopes have been identified to date. To gain insight into the HLA-A3.1-restricted T cell epitope repertoire of human melanoma, we analyzed the immunologic reactivity of CTLs isolated from tumor-involved or tumor-free lymph nodes in two HLA-A3.1+ melanoma patients. Three CTL lines, clonal or highly oligoclonal in their TCR composition, and two CTL clones were selected for HLA class I-restricted lysis of the autologous tumor and then tested for the recognition of HLA-A3+ and HLA-A3- normal or neoplastic cells of the melanocyte lineage. One CTL recognized a unique HLA-A3.1-restricted Ag expressed only by the autologous tumors, while all the other CTLs defined three HLA-A3.1 epitopes shared by melanomas, but not by melanocytes. Moreover, the epitopes of two CTL lines with different specificity were reconstituted by nonoverlapping fractions of HLA-A3+ melanoma-derived peptides resolved by reverse phase-HPLC, indicating that distinct naturally processed peptides were specifically recognized on melanoma cells in association with HLA-A3.1 molecules. These novel lineage-unrelated HLA-A3.1-restricted melanoma epitopes do not derive from MAGE, BAGE, or GAGE gene families, as evaluated by the COS-7 transfection assay. Our data show that CTLs may recognize HLA-A3.1-class I complexes presenting melanoma (but not melanocyte)-associated epitopes that are either unique to a given patient's tumor or that are shared between multiple melanomas.
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M3 - Article
C2 - 8816412
AN - SCOPUS:0030267510
VL - 157
SP - 3030
EP - 3038
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -