Linked Life Data

9469433

Source:http://linkedlifedata.com/resource/pubmed/id/9469433

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-2-26
pubmed:abstractText
The Melan-A/MART-1 gene, which is expressed by normal melanocytes as well as by most fresh melanoma samples and melanoma cell lines, codes for Ags recognized by tumor-reactive CTL. HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides. The sequences of these two peptides are not necessarily optimal as far as binding to HLA-A*0201 is concerned, since both lack one of the dominant anchor amino acid residues (leucine or methionine) at position 2. In this study we introduced single amino acid substitutions in either one of the two natural peptide sequences with the aim of improving peptide binding to HLA-A*0201 and/or recognition by specific CTL. Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL. In contrast, among the Melan-A(26-35) peptide analogues tested, the peptide ELAGIGILTV was not only able to display stable binding to HLA-A2.1 but was also recognized more efficiently than the natural peptide by two short-term cultured tumor-infiltrated lymph node cell cultures as well as by five of five tumor-reactive CTL clones. Moreover, in vitro generation of tumor-reactive CTL by stimulation of PBMC from HLA-A*0201 melanoma patients with this particular peptide analogue was much more efficient than that observed with either one of the two natural peptides. These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
160
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1750-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:9469433-Antigens, Neoplasm, pubmed-meshheading:9469433-Cell Line, Transformed, pubmed-meshheading:9469433-Cells, Cultured, pubmed-meshheading:9469433-Clone Cells, pubmed-meshheading:9469433-Cytotoxicity, Immunologic, pubmed-meshheading:9469433-Epitopes, T-Lymphocyte, pubmed-meshheading:9469433-HLA-A Antigens, pubmed-meshheading:9469433-Humans, pubmed-meshheading:9469433-Immunodominant Epitopes, pubmed-meshheading:9469433-Lymph Nodes, pubmed-meshheading:9469433-Lymphocyte Activation, pubmed-meshheading:9469433-Lymphocytes, Tumor-Infiltrating, pubmed-meshheading:9469433-MART-1 Antigen, pubmed-meshheading:9469433-Melanoma, pubmed-meshheading:9469433-Neoplasm Proteins, pubmed-meshheading:9469433-Peptide Fragments, pubmed-meshheading:9469433-T-Lymphocytes, Cytotoxic, pubmed-meshheading:9469433-Tumor Cells, Cultured
pubmed:year
1998
pubmed:articleTitle
Enhanced generation of specific tumor-reactive CTL in vitro by selected Melan-A/MART-1 immunodominant peptide analogues.
pubmed:affiliation
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland. danila.valmori@isrec.unil.ch
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't