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Overlapping peptides of melanocyte differentiation antigen melan‐A/MART‐1 recognized by autologous cytolytic T lymphocytes in association with HLA‐B45.1 and HLA‐A2.1
Author(s) -
Schneider Jörg,
Brichard Vincent,
Boon Thierry,
Meyer zum Büschenfelde KarlHermann,
Wölfel Thomas
Publication year - 1998
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/(sici)1097-0215(19980130)75:3<451::aid-ijc20>3.0.co;2-a
Subject(s) - ctl* , epitope , human leukocyte antigen , peptide , biology , cytolysis , antigen , microbiology and biotechnology , immunology , cytotoxic t cell , virology , cd8 , genetics , biochemistry , in vitro
From the peripheral blood lymphocytes (PBLs) of melanoma patient SK29(AV) we have previously isolated 2 independent cytolytic T lymphocyte (CTL) clones (CTL7/147 and CTL13/211), which lysed autologous tumor cells in association with HLA‐B45.1. As demonstrated here, both CTL clones were directed against melanocyte differentiation antigen Melan‐A/MART‐1, which also was recognized by HLA‐A2.1‐restricted CTLs from the same patient. By generating and transfecting 3′‐deletion mutants of Melan‐A/MART‐1 cDNA, we localized its peptide‐coding regions. The HLA‐B45.1‐presented peptides were derived from a hydrophobic region of the protein and largely overlapped the peptides recognized by CTLs from the same patient in association with HLA‐A2.1. We determined the fine specificity of these CTL clones with synthetic peptides. CTL clone CTL7/147 recognized the 11‐mer peptide AEEAAGIGILT (residues 24–34) at the lowest concentrations. The absence of threonine‐34 abrogated the recognition by CTL7/147. The truncated peptide AEEAAGIGIL (residues 24–33) proved to be the optimal synthetic peptide for sensitization against lysis by CTL13/211. This indicated that C‐terminal threonine‐34 was not involved in binding to HLA‐B45.1 but, rather, was part of the epitope for CTL7/147. HLA‐B45.1‐associated peptides of Melan‐A/MART‐1 were regularly processed and presented by other melanomas and other cell types. Three of 4 independent HLA‐A2.1‐restricted SK29‐CTL clones recognized the 10‐mer peptide EAAGIGILTV (residues 26–35) at 10‐ to 100‐fold lower concentrations than the nonamer AAGIGILTV (residues 27–35), previously described as the common immunodominant peptide antigen for all known anti‐Melan‐A/MART‐1 CTLs restricted by HLA‐A2.1. Different melanoma peptide antigens currently are applied in therapeutic vaccination studies. Our findings emphasize that restricting to peptides of minimal length might exclude relevant T‐cell epitopes. Int. J. Cancer 75:451–458, 1998. © 1998 Wiley‐Liss, Inc.