High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals
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Version: author
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
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
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 12:13
Last modification date
20/08/2019 15:44