Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation
| Autor: | Robert A. Henderson, John A. Hural, Michael D. Kalos, Andria McNabb, Rachel S. Friedman, Sean S. Steen |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Immunology Tissue kallikrein Molecular Sequence Data Epitopes T-Lymphocyte Biology Cell Fractionation Lymphocyte Activation Epitope law.invention Prostate cancer stomatognathic system Prostate law medicine Tumor Cells Cultured Immunology and Allergy Humans Amino Acid Sequence Gene Conserved Sequence Cell Line Transformed Antigen Presentation HLA-D Antigens Hybridomas Kallikrein Prostate-Specific Antigen medicine.disease Molecular biology Immunity Innate Peptide Fragments Recombinant Proteins Clone Cells Prostate-specific antigen medicine.anatomical_structure Multigene Family Recombinant DNA Leukocytes Mononuclear Female Kallikreins |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 169(1) |
| ISSN: | 0022-1767 |
| Popis: | Kallikrein (KLK)4 is a recently described member of the tissue kallikrein gene family that is specifically expressed in normal and prostate tumor tissues. The tissue-specific expression profile of this molecule suggests that it might be useful as a vaccine candidate against prostate cancer. To examine the presence of CD4 T cells specific for KLK4 in PBMC of normal individuals, a peptide-based in vitro stimulation protocol was developed that uses overlapping KLK4-derived peptides spanning the majority of the KLK4 protein. Using this methodology, three naturally processed CD4 epitopes derived from the KLK4 sequence are identified. These epitopes are restricted by HLA-DRB1*0404, HLA-DRB1*0701, and HLA-DPB1*0401 class II alleles. CD4 T cell clones specific for these epitopes are shown to efficiently and specifically recognize both recombinant KLK4 protein and lysates from prostate tumor cell lines virally infected to express KLK4. CD4 T cells specific for these KLK4 epitopes are shown to exist in PBMC from multiple male donors that express the relevant class II alleles, indicating that a CD4 T cell repertoire specific for KLK4 is present and potentially expandable in prostate cancer patients. The demonstration that KLK4-specific CD4 T cells exist in the peripheral circulation of normal male donors and the identification of naturally processed KLK4-derived CD4 T cell epitopes support the use of KLK4 in whole gene-, protein-, or peptide-based vaccine strategies against prostate cancer. Furthermore, the identification of naturally processed KLK4-derived epitopes provides valuable tools for monitoring preexisting and vaccine-induced responses to this molecule. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|