title: Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes.
abstract: We and others have previously reported that melanoma-specific, cytotoxic T lymphocytes (CTL) define a minimum of six class I-presented peptide epitopes common to most HLA-A2+ melanomas. Here we show that three of these peptide epitopes are coordinately recognized by a CTL clone obtained by limiting dilution from the peripheral blood of an HLA-A2+ melanoma patient. Tandem mass spectrometry was used to characterize and sequence one of these three naturally processed melanoma peptides. One of the potential forms of the deduced peptide sequence (XXTVXXGVX, X = I or L) matches positions 32-40 of the recently identified melanoma gene MART-1/Melan-A. This peptide (p939; ILTVILGVL) binds to HLA-A2 with an intermediate-to-low affinity and is capable of sensitizing the HLA-A2+ T2 cell line to lysis by CTL lines and clones derived from five different melanoma patients. A relative high frequency of anti-p939-specific effector cells appear to be present in situ in HLA-A2+ melanoma patients, since p939 is also recognized by freshly isolated tumor infiltrating lymphocytes. p939 represents a good candidate for the development of peptide-based immunotherapies for the treatment of patients with melanoma.
authors: Istituto Nazionale Tumori, Milan, Italy.
authors: C
authors: C
authors: Castelli
authors: W J
authors: WJ
authors: Storkus
authors: M J
authors: MJ
authors: Maeurer
authors: D M
authors: DM
authors: Martin
authors: E C
authors: EC
authors: Huang
authors: B N
authors: BN
authors: Pramanik
authors: T L
authors: TL
authors: Nagabhushan
authors: G
authors: G
authors: Parmiani
authors: M T
authors: MT
authors: Lotze
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D018604:Epitope Mapping; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D013058:Mass Spectrometry; D008545:Melanoma / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D010455:Peptides