High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals

Details

Ressource 1Download: BIB_8543B820A159.P001.pdf (166.08 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_8543B820A159
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals
Journal
Journal of Experimental Medicine
Author(s)
Pittet  M. J., Valmori  D., Dunbar  P. R., Speiser  D. E., Lienard  D., Lejeune  F., Fleischhauer  K., Cerundolo  V., Cerottini  J. C., Romero  P.
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
09/1999
Volume
190
Number
5
Pages
705-15
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 6
Abstract
Using fluorescent HLA-A*0201 tetramers containing the immunodominant Melan-A/MART-1 (Melan-A) tumor-associated antigen (Ag), we previously observed that metastatic lymph nodes of melanoma patients contain high numbers of Ag-experienced Melan-A-specific cytolytic T lymphocytes (CTLs). In this paper, we enumerated and characterized ex vivo Melan-A-specific cells in peripheral blood samples from both melanoma patients and healthy individuals. High frequencies (>/=1 in 2,500 CD8(+) T cells) of Melan-A-specific cells were found in 10 out of 13 patients, and, surprisingly, in 6 out of 10 healthy individuals. Virtually all Melan-A-specific cells from 6 out of 6 healthy individuals and from 7 out of 10 patients displayed a naive CD45RA(hi)/RO(-) phenotype, whereas variable proportions of Ag-experienced CD45RA(lo)/RO(+) Melan-A-specific cells were observed in the remaining 3 patients. In contrast, ex vivo influenza matrix-specific CTLs from all individuals exhibited a CD45RA(lo)/RO(+) memory phenotype as expected. Ag specificity of tetramer-sorted A2/Melan-A(+) cells from healthy individuals was confirmed after mitogen-driven expansion. Likewise, functional limiting dilution analysis and interferon gamma ELISPOT assays independently confirmed that most of the Melan-A-specific cells were not Ag experienced. Thus, it appears that high frequencies of naive Melan-A-specific CD8(+) T cells can be found in a large proportion of HLA-A*0201(+) individuals. Furthermore, as demonstrated for one patient followed over time, dramatic phenotype changes of circulating Melan-A-specific cells can occur in vivo.
Keywords
Adult Aged *Antigens, Neoplasm CD8-Positive T-Lymphocytes/*immunology Case-Control Studies HLA-A2 Antigen/chemistry/*genetics Humans Immunologic Memory Interferon Type II/biosynthesis Lymphocyte Count Melanoma/genetics/*immunology/secondary Middle Aged Neoplasm Proteins/*immunology Phenotype Protein Conformation Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:13
Last modification date
20/08/2019 14:44
Usage data