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Identification of a new HLA‐A*0201‐restricted T‐cell epitope from the tyrosinase‐related protein 2 (TRP2) melanoma antigen
Author(s) -
Sun Yuansheng,
Song Mingxia,
Stevanović Stefan,
Jankowiak Carsten,
Paschen Annette,
Rammensee HansGeorg,
Schadendorf Dirk
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000801)87:3<399::aid-ijc14>3.0.co;2-9
Subject(s) - cytotoxic t cell , epitope , human leukocyte antigen , antigen , cd8 , immunology , melanoma , biology , immunotherapy , ctl* , t cell , microbiology and biotechnology , cancer research , immune system , in vitro , genetics
For the development of peptide‐based immunotherapies, the identification of additional tumor antigens and T‐cell epitopes is required. Because HLA‐A*0201 is the most common allele in Caucasians, who represent the majority of patients with melanomas, 6 peptides carrying an HLA‐A*0201 motif were synthesized from tyrosinase‐related protein‐2 (TRP2) melanoma antigen and tested for binding affinity to the HLA allele using processing‐defective T2 cells. These peptides were then pulsed onto autologous dendritic cells and used to stimulate in vitro CD8 + ‐enriched T cells isolated from peripheral blood of HLA‐A*02 + healthy donors or melanoma patients for the induction of specific cytotoxic T lymphocytes (CTLs). One peptide, TRP2 288–296 (SLDDYNHLV), the best HLA‐A*0201 binder, elicited specific CTLs from 1 of 4 patients and 3 of 4 healthy donors. The induced CTLs from the patient and from 1 donor efficiently recognized HLA‐A*02 + TRP2 + melanomas as well as COS‐7 cells expressing HLA‐A*0201 and TRP2 in an HLA class I–restricted manner, as assessed by cytokine production and direct cytolysis. The remaining 2 CTL lines derived from 2 donors displayed low T‐cell receptor avidity, which could lyse melanoma cells in the presence of exogenous peptide. Since TRP2 is an antigen expressed in most melanomas, identification of the TRP2/HLA‐A*0201 peptide SLDDYNHLV may facilitate the design of present peptide‐based immunotherapies for the treatment of a large fraction of melanoma patients. Int. J. Cancer 87:399–404, 2000. © 2000 Wiley‐Liss, Inc.