Functional analysis of HLA-A*0201/Melan-A peptide multimer+ CD8+ T cells isolated from an HLA-A*0201- donor: exploring tumor antigen allorestricted recognition.

Details

Serval ID
serval:BIB_C791D048644E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional analysis of HLA-A*0201/Melan-A peptide multimer+ CD8+ T cells isolated from an HLA-A*0201- donor: exploring tumor antigen allorestricted recognition.
Journal
Cancer Immunity
Author(s)
Dutoit V., Guillaume P., Romero P., Cerottini J.C., Valmori D.
ISSN
1424-9634[electronic]
Publication state
Published
Issued date
2002
Volume
2
Pages
7
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Recent studies in mouse models have suggested that genetic transfer of tumor antigen-specific high affinity T cell receptors (TCR) into host lymphocytes could be a viable strategy for the rapid induction of tumor-specific immunity. A previously proposed approach for the isolation of such TCRs consists in circumventing tolerance to self-restricting HLA/peptide complexes by deriving them from PMBCs of allogenic donors. Towards this aim, we used fluorescent HLA-A2 class-I/peptide soluble multimers to isolate A2-restricted CD8+ T cells specific for a previously described Melan-A peptide enhanced analog (Melan-A 26-35 A27L) from an HLA-A*0201 (A2) negative donor. We isolated two distinct groups of Melan-A 26-35 A27L-specific clones. Clones from the first group recognized the analog peptide with high avidity but showed very low recognition of Melan-A parental peptides. In contrast, clones from the second group efficiently recognized Melan-A parental peptides. Surprisingly however, most clones recognized not only A2+ Melan-A+ targets, but also A2+ Melan-A- targets suggesting that they can also recognize endogenous peptides other than Melan-A. In addition, one clone showed full cross-recognition of an antigenically unrelated peptide. Together, our data show that HLA-A2/peptide multimers can be successfully used for the isolation of allorestricted CD8+ T cells reactive with tumor antigen-derived peptides. However, as the cross-reactivity of these apparently peptide-specific allorestricted TCRs is presently unpredictable, a careful in vitro analysis of their reactivity to the host's normal cells is recommended.
Keywords
Animals, Antigens, Neoplasm/immunology, CD8-Positive T-Lymphocytes/immunology, HLA-A Antigens/immunology, Humans, Melanoma/pathology, Mice, Neoplasm Proteins/immunology, Tumor Cells, Cultured
Pubmed
Create date
28/01/2008 11:14
Last modification date
20/08/2019 15:42
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