T cell response against stress proteins

我们以前曾报道过70 kDa的热休克同源蛋白样分子（hsc 70）在大鼠成纤维细胞肿瘤转化过程中沿着表达于细胞表面，并以MHC I类不受限制的方式被CD 3 ^+、CD 4 ^-、CD 8 ^-、NKR-P1^-和TCR-<alpha>β ^- T（DNT）杀伤细胞识别。我们研究了hsc 70和DNT细胞之间相互作用的机制。H-ras癌基因转化的大鼠纤维肉瘤W31细胞在常规的5%FCS（5%W31）中生长时在细胞表面上表达hsc 70，其密度与在1%FCS（1%W31）中细胞生长被抑制时几乎相同。但DNT细胞仅裂解5%W31，而不裂解1%W31。由于这些观察结果提示快速生长的W31细胞的某些肽Ag可能在hsc 70和DNT细胞之间的相互作用中起作用，我们用三氟乙酸（TFA）提取的分子大小小于3000 Da的快速生长的W31肿瘤Ag推动1%W31细胞。我们还用TFA提取的来自中等生长的W14肿瘤和整个胎儿组织的Ag脉冲1%W31。我们的数据表明，DNT细胞对仅用TFA提取的来自W31肿瘤的Ag推动的1%W31具有明显的细胞毒性。抗大鼠hsc 70 mAb完全阻断这种细胞毒性。此外，链霉蛋白酶K处理Ags明显抑制DNT细胞的细胞毒性。综上所述，这些数据表明，肽Ag和hsc 70的复合物参与了hsc 70和DNT细胞之间的细胞毒性机制。

We previously reported that the 70kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3^+, CD4^-, CD8^-, NKR-P1^-, and TCR-_<alpha> beta^- T (DNT) killer cells in an MHC class Iunrestricted fashion. We investigated the mechanism of interaction between hsc70 and DNT cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on the cell surface in almost the same density when the cells were growing in a conventional 5%FCS (5%W31) as when the cell growth was inhibited in the cultivation with 1%FCS (1%W31) . However, DNT cells lysed only 5%W31, but not 1%W31. Since these observations suggest that certain peptide Ags of the fast growing W31 cells may play a role in the interacyion between hsc70 and DNT cells, we pushed 1%W31 cells with trifluoroacetic acid (TFA) -extracted fast growing W31 tumor Ags of less than 3000 Da in molecular size. We also pulsed 1%W31 with TFA-extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data indicated that DNT cells were clearly cytotoxic to 1%W31 pushed only with TFA-extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this cytotoxicity. In addtion, pronase K treatment of Ags clearly inhibited the cytotoxicity by DNT cells. Taken together, these data suggest that the complex of peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT cells.