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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3105-3113.
Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2005-04-1487.


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IMMUNOBIOLOGY

Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells

Frank Neumann, Claudia Wagner, Klaus-Dieter Preuss, Boris Kubuschok, Claudia Schormann, Stefan Stevanovic, and Michael Pfreundschuh

From Medizinische Klinik I, Saarland University Medical School, Homburg, Germany; and Institute for Cell Biology, Department of Immunology, EberhardKarls-Universität, Tübingen, Germany.

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.


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