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.
Details
Serval ID
serval:BIB_DE716DD57709
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Journal of immunology
ISSN
0022-1767
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
177
Number
10
Pages
6769-6779
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
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
Create date
28/01/2008 12:14
Last modification date
20/08/2019 17:03