Abstract
Natural antigen processing and presentation of antigen is thought to be important for the generation of a broad functional repertoire of antigen-specific T cells. In this study, the T-cell repertoire to an immunodominant human leukocyte antigen A2 (HLA-A2) binding peptide epitope of HER-2/neu, p369-377, was examined in a patient following immunization with a peptide-based vaccine consisting of helper peptides encompassing HLA-A2 peptide epitopes. The responding T-cell repertoire generated was both phenotypically and functionally diverse. A total of 21 p369-377 clones were generated from this patient. With the exception of two clones, all clones were CD3+. Sixteen of the clones were CD8+/CD4-. Five of the clones were CD4+/CD8-, despite being generated with an HLA-A2 binding peptide. Nineteen of 21 of clones expressed the αβ-T-cell receptor (TCR). The remaining two clones expressed the γδ T-cell response (TCR). Selected αβ-TCR clones, both CD8+ and CD4+, could lyse HLA-A2 transfected HER2 over-expressing tumor cells and p369-377-loaded B-lymphoblastic cell line. In addition to their lytic capabilities these clones could be induced to produce interferon-γ (IFN-γ) specifically in response to p369-377 peptide stimulation. The 2 γδ-TCR clones expressed CD8 and lysed HLA-A2+ HER-2/neu tumor cells, but not HLA-A2- HER-2/neu+ tumor cells. One of γδ-TCR clones also released IFN-γ directly in response to p369-377 stimulation. These results suggest that a tumor antigen TCR, directed against a specific epitope, can be markedly polyclonal at multiple levels including CD4/CD8 and TCR.
Original language | English (US) |
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Pages (from-to) | 547-557 |
Number of pages | 11 |
Journal | Human Immunology |
Volume | 63 |
Issue number | 7 |
DOIs | |
State | Published - 2002 |
Keywords
- CTL
- T lymphocytes
- Tumor immunity
- Vaccination
- γδ T cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology