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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-2-20
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
451-8
pubmed:dateRevised
2011-5-23
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
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.
pubmed:affiliation
I Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität, Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't