Novel soluble HLA-A2/MELAN-A complexes selectively stain a differentiation defective subpopulation of CD8+ T cells in patients with melanoma.

Détails

ID Serval
serval:BIB_32E1A9FD881A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Novel soluble HLA-A2/MELAN-A complexes selectively stain a differentiation defective subpopulation of CD8+ T cells in patients with melanoma.
Périodique
International Journal of Cancer
Auteur(s)
Guillaume P., Baumgaertner P., Neff L., Rufer N., Wettstein P., Speiser D.E., Luescher I.F.
ISSN
1097-0215[electronic], 0020-7136[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
127
Numéro
4
Pages
910-923
Langue
anglais
Résumé
Multimeric MHC I-peptide complexes containing phycoerythrin-streptavidin are widely used to detect and investigate antigen-specific CD8+ (and CD4+) T cells. Because such reagents are heterogeneous, we compared their binding characteristics with those of monodisperse dimeric, tetrameric and octameric complexes containing linkers of variable length and flexibility on Melan-A-specific CD8+ T cell clones and peripheral blood mononuclear cells (PBMC) from HLA-A*0201(+) melanoma patients. Striking binding differences were observed for different defined A2/Melan-A(26-35) complexes on T cells depending on their differentiation stage. In particular, short dimeric but not octameric A2/Melan-A(26-35) complexes selectively and avidly stained incompletely differentiated effector-memory T cells clones and populations expressing CD27 and CD28 and low levels of cytolytic mediators (granzymes and perforin). This subpopulation was found in PBMC from all six melanoma patients analyzed and proliferated on peptide stimulation with only modest phenotypic changes. By contrast influenza matrix(58-66) -specific CD8+ PBMC from nine HLA-A*0201(+) healthy donors were efficiently stained by A2/Flu matrix(58-61) multimers, but not dimer and upon peptide stimulation proliferated and differentiated from memory into effector T cells. Thus PBMC from melanoma patients contain a differentiation defective sub-population of Melan-A-specific CD8+ T cells that can be selectively and efficiently stained by short dimeric A2/Melan- A(26-35) complexes, which makes them directly accessible for longitudinal monitoring and further investigation.
Mots-clé
Antigens, Neoplasm/metabolism, CD8-Positive T-Lymphocytes/immunology, Case-Control Studies, Cell Differentiation, Dimerization, Flow Cytometry, HLA-A Antigens/metabolism, Humans, Immunologic Memory/immunology, MART-1 Antigen, Melanoma/immunology, Melanoma/pathology, Neoplasm Proteins/metabolism, Peptide Fragments/immunology, Peptide Fragments/metabolism, Receptors, Antigen, T-Cell/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/01/2010 15:02
Dernière modification de la notice
20/08/2019 13:18
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