Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.

Détails

ID Serval
serval:BIB_DE716DD57709
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.
Périodique
Journal of immunology
Auteur(s)
Bioley G., Jandus C., Tuyaerts S., Rimoldi D., Kwok W.W., Speiser D.E., Tiercy J.M., Thielemans K., Cerottini J.C., Romero P.
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
177
Numéro
10
Pages
6769-6779
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Over the past decade, many efforts have been made to identify MHC class II-restricted epitopes from different tumor-associated Ags. Melan-A/MART-1(26-35) parental or Melan-A/MART-1(26-35(A27L)) analog epitopes have been widely used in melanoma immunotherapy to induce and boost CTL responses, but only one Th epitope is currently known (Melan-A51-73, DRB1*0401 restricted). In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients. These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301. CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway. This suggests that the epitopes are naturally processed and presented by EBV-B cells and melanoma cells. Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1. Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients. Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient. Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.
Mots-clé
Amino Acid Sequence, Antigen Presentation, Antigens, Neoplasm/blood, Antigens, Neoplasm/immunology, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/immunology, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, Cell Separation, Clone Cells, Epitopes, T-Lymphocyte/blood, Epitopes, T-Lymphocyte/immunology, HLA-D Antigens/chemistry, HLA-D Antigens/immunology, HLA-DQ Antigens/immunology, HLA-DQ Antigens/metabolism, Humans, Melanoma/blood, Melanoma/immunology, Membrane Glycoproteins/immunology, Membrane Glycoproteins/metabolism, Molecular Sequence Data, Neoplasm Proteins/blood, Neoplasm Proteins/immunology, Peptide Fragments/chemical synthesis, Peptide Fragments/immunology, Signal Transduction/immunology
Pubmed
Web of science
Création de la notice
28/01/2008 12:14
Dernière modification de la notice
20/08/2019 17:03
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