title: Shared epitopes for HLA-A3-restricted melanoma-reactive human CTL include a naturally processed epitope from Pmel-17/gp100.
abstract: Human CD8+ CTL recognize peptides bound to class I MHC molecules on the surface of melanoma cells. Several peptides derived from melanocyte lineage-specific proteins have been identified as epitopes for HLA-A2 restricted melanoma-reactive CTL. Because less than half of melanoma patients express HLA-A2, it is important to identify CTL epitopes restricted by other common MHC molecules including HLA-A1 and -A3. We have generated HLA-A3-restricted human CTL that recognize one or more shared melanoma Ags. All of the melanomas recognized by one of these CTL lines express Pmel-17/gp100, and those that fail to express this Ag are not lysed. This CTL line also specifically recognizes the lymphoblastoid line C1R-A3 following infection with a recombinant vaccinia encoding the melanocyte lineage-specific protein Pmel-17/gp100. Thus, at least one Pmel-17/ gp100 peptide is an epitope for this CTL line. We have identified ALLAVGATK (Pmel-17/gp100 residues 17-25) as an epitope for this CTL line and have shown that it is naturally processed and presented by HLA-A3 on melanoma cells. A second HLA-A3-restricted melanoma-reactive CTL line recognizes at least one additional shared epitope. These findings suggest that cellular immune responses directed against multiple shared melanoma epitopes exist in the 20 to 25% of melanoma patients who express HLA-A3. In addition, immunotherapy directed against Pmel-17/gp100 and other shared melanoma Ags may be useful in a large subset of these patients.
authors.affiliation: Department of Microbiology, University of Virginia, Charlottesville 22908, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Skipper
authors.forename: D J
authors.initials: DJ
authors.lastname: Kittlesen
authors.forename: R C
authors.initials: RC
authors.lastname: Hendrickson
authors.forename: D D
authors.initials: DD
authors.lastname: Deacon
authors.forename: N L
authors.initials: NL
authors.lastname: Harthun
authors.forename: S N
authors.initials: SN
authors.lastname: Wagner
authors.forename: D F
authors.initials: DF
authors.lastname: Hunt
authors.forename: V H
authors.initials: VH
authors.lastname: Engelhard
authors.forename: C L
authors.initials: CL
authors.lastname: Slingluff
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000378:metabolism*; D015791:HLA-A3 Antigen; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D015791:HLA-A3 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D011506:Proteins; D058951:gp100 Melanoma Antigen