Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells
| Autor: | Frank Neumann, Boris Kubuschok, Klaus-Dieter Preuss, Claudia Wagner, Michael Pfreundschuh, Stefan Stevanovic, Claudia Schormann |
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| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Tumor suppressor gene medicine.medical_treatment Molecular Sequence Data Immunology Antigen presentation Biology Major histocompatibility complex Biochemistry Epitope Epitopes Testicular Neoplasms Antigens Neoplasm medicine Humans Amino Acid Sequence Antigen Presentation Nuclear Proteins Dendritic Cells Cell Biology Hematology Immunotherapy medicine.disease Molecular biology Peripheral T-cell lymphoma DNA-Binding Proteins Peptide vaccine biology.protein Cancer/testis antigens |
| Zdroj: | Blood. 106:3105-3113 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Because of their frequent expression in a wide spectrum of malignant tumors but not in normal tissue except testis, cancer testis antigens are promising targets. However, except for HOM-TES-14/SCP1, their expression in malignant lymphomas is rare. SCP1 (synaptonemal complex protein 1) has been shown to elicit antibody responses in the autologous host, but no T-cell responses against HOM-TES-14/SCP1 have been reported. Using the SYFPEITHI algorithm, we selected peptides with a high binding affinity to major histocompatibility complex class 2 (MHC 2) molecules. The pentadecamer epitope p635-649 induced specific CD4+ T-cell responses that were shown to be restricted by HLA-DRB1*1401. The responses could be blocked by preincubation of T cells with anti-CD4 and antigen-presenting cells with anti–HLA-DR, respectively, proving the HLA-DR–restricted presentation of p635-649 and a CD4+ T-cell–mediated effector response. Responding CD4+ cells did not secrete interleukin-5 (IL-5), indicating that they belong to the TH1 subtype. The natural processing and presentation of p635-649 were demonstrated by pulsing autologous and allogeneic dendritic cells with a protein fragment covering p635-649. Thus, p635-649 is the first HOM-TES-14/SCP1–derived epitope to fulfill all prerequisites for use as a peptide vaccine in patients with HOM-TES-14/SCP1–expressing tumors, which is the case in two thirds of peripheral T-cell lymphomas. |
| Databáze: | OpenAIRE |
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