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Epitope hierarchy of spontaneous CD4+ T cell responses to LAGE-1.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Jan 01; Vol. 186 (1), pp. 312-22. Date of Electronic Publication: 2010 Dec 03. - Publication Year :
- 2011
-
Abstract
- NY-ESO-1 and LAGE-1 represent highly homologous cancer-germline Ags frequently coexpressed by many human cancers, but not by normal tissues, except testis. In contrast to NY-ESO-1, little is known about spontaneous immune responses to LAGE-1. In the current study, we report on spontaneous LAGE-1-specific CD4(+) T cells isolated from PBLs of patients with advanced LAGE-1(+)/NY-ESO-1(+) melanoma and directed against three promiscuous and immunodominant epitopes. Strikingly, although the three LAGE-1-derived epitopes are highly homologous to NY-ESO-1-derived epitopes, LAGE-1-specific CD4(+) T cells did not cross-react with NY-ESO-1. LAGE-1-specific CD4(+) T cells produced Th1-type and/or Th2-type cytokines and did not exert inhibitory effects on allogenic T cells. We observed that most patients with spontaneous NY-ESO-1-specific responses exhibited spontaneous CD4(+) T cell responses to at least one of the three immunodominant LAGE-1 epitopes. Additionally, nearly half of the patients with spontaneous LAGE-1-specific CD4(+) T cell responses had circulating LAGE-1-specific Abs that recognized epitopes located in the C-terminal portion of LAGE-1, which is distinct from NY-ESO-1. Collectively, our findings define the hierarchy of immunodominance of spontaneous LAGE-1-specific CD4(+) T cell responses in patients with advanced melanoma. These findings demonstrate the capability of LAGE-1 to stimulate integrated cellular and humoral immune responses that do not cross-react with NY-ESO-1. Therefore, they provide a strong rationale for the inclusion of LAGE-1 peptides or protein in vaccine trials for patients with NY-ESO-1(+)/LAGE-1(+) tumors.
- Subjects :
- Amino Acid Sequence
Animals
Antigens, Neoplasm chemistry
Antigens, Surface chemistry
CD4-Positive T-Lymphocytes chemistry
COS Cells
Cancer Vaccines immunology
Cell Line, Tumor
Chlorocebus aethiops
Epitopes, T-Lymphocyte chemistry
Humans
Immunodominant Epitopes chemistry
Melanoma chemistry
Melanoma immunology
Melanoma pathology
Membrane Proteins chemistry
Membrane Proteins immunology
Molecular Sequence Data
Peptide Fragments immunology
Peptide Fragments metabolism
Protein Binding immunology
Antigens, Neoplasm immunology
Antigens, Surface immunology
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
Epitopes, T-Lymphocyte immunology
Immunodominant Epitopes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 186
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21131422
- Full Text :
- https://doi.org/10.4049/jimmunol.1001989