Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells.
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 T(H)1 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.
Neumann
Frank
F
Medizinische Klinik I, Saarland University Medical School, D-66421 Homburg/Saar, Germany.
Wagner
Claudia
C
Preuss
Klaus-Dieter
KD
Kubuschok
Boris
B
Schormann
Claudia
C
Stevanovic
Stefan
S
Pfreundschuh
Michael
M
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000276:immunology*; D013736:Testicular Neoplasms / Q000276:immunology*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000939:Epitopes; D009687:Nuclear Proteins; C489753:SYCP1 protein, human