Identification of novel helper epitopes of MAGE-A4 tumour antigen: useful tool for the propagation of Th1 cells

MAGE-A4 has been considered as an attractive cancer-testis (CT) antigen for tumour immunotherapy. It has been well accepted that T-helper type 1 (Th1) cell-dominant immunity is critical for the successful induction of antitumour immunity in a tumour-bearing host. The adoptive Th1 cell therapy has been shown to be an attractive strategy for inducing tumour eradication in mouse systems. However, Th1-cell therapy using human tumour-specific Th1 cells, which were expanded from peripheral blood mononuclear cells (PBMCs) in a clinically useful protocol, has never been performed. Here, we first identified MAGE-A4-derived promiscuous helper epitope, peptide (MAGE-A4 280–299), bound to both HLA-DPB1*0501 and DRB1*1403. Using the peptide, we established a suitable protocol for the propagation of MAGE-A4-specific Th1 cells in vitro. Culture of CD4+ T cells with IFN-γ-treated PBMC-derived adherent cells in the presence of helper epitope peptide resulted in a great expansion of MAGE-A4-reactive Th cells producing IFN-γ , but not IL-4. Moreover, it was shown that ligation of MAGE-A4-reactive Th1 cells with the cognate peptide caused the production of IFN-γ and IL-2. Thus, our identified MAGE-A4 helper epitope peptide will become a good tool for the propagation of tumour-specific Th1 cells applicable to adoptive immunotherapy of human cancer

Martensitic Transformations and Shape Memory Effect in Ti-Ni Sputter-Deposited Thin Films

Films deposited on quartz substrates by sputtering in an argon atmosphere using a sputtering target of a equiatomic TiNi alloy were investigated by differential scanning calorimetry and electron microscopy. The substrate temperature was kept below 423K during sputtering. Transmission electron microscope observation showed that the as-deposited films are amorphous and they crystallize by heating above 750K.The amorphous films were heat treated at various temperatures between 573 and 993K for crystallization. The composition of the films were determined by electron probe micro analysis using a calibration line prepared from bulk samples of well-established compositions. For it was found that Ti content decreases by sputtering, film composition was controlled by placing Ti pieces on the target and changing their sizes. In this way it was successful to obtain films of various composition. By the crystallization heat treatment, no precipitation occurred in the 50.0at%Ti-Ni film, whereas T i 2Ni precipitated in the 53.2at%Ti-Ni and 51.6at% Ti-Ni foils, and Ti3Ni4 precipitated in the 48.6at%Ti-Ni film. The R-phase transformation occurred reversibly on cooling and heating these films in the electron microscope. It was confirmed by constant load thermal cycling tests that the films show a very good shape memory