Szea Daniel M Y, Brown Ross D, Yang Shihong, Gibson John, Ho Joy, Fazekas de St Groth Barbara, Basten Antony, Joshua Douglas E
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
Leuk Lymphoma. 2003 Sep;44(9):1557-68. doi: 10.3109/10428190309178780.
Idiotypic determinants are potential patient-specific tumor antigens in multiple myeloma (MM). In this study, we have determined the DNA sequence of the variable region of the tumor immunoglobulin (Ig) in 6 patients with MM. We then selected high affinity class I-restricted T-cell peptide epitopes in tumor Ig using two different internet-based epitope prediction programs. High affinity binding peptides were identified by at least one program in 4 out of 6 patients. Of these 35 peptides, only 3 scored high by both analyses. Given that all 6 patients had expanded T-cell clones with a cytotoxic (CD57+CD8+CD28-perforin+) phenotype, known to be associated with a longer survival and postulated to recognise tumor epitopes, this analysis indicates that such clones are unlikely to be exclusively directed towards tumor immuoglobulin, and suggests the need to expand the scope of the search for tumor epitopes with the ability to stimulate cytotoxic T cells in vivo.
独特型决定簇是多发性骨髓瘤（MM）中潜在的患者特异性肿瘤抗原。在本研究中，我们测定了6例MM患者肿瘤免疫球蛋白（Ig）可变区的DNA序列。然后，我们使用两个不同的基于互联网的表位预测程序，在肿瘤Ig中选择了高亲和力的I类限制性T细胞肽表位。6例患者中有4例通过至少一个程序鉴定出高亲和力结合肽。在这35个肽中，只有3个在两项分析中得分都很高。鉴于所有6例患者都有具有细胞毒性（CD57 + CD8 + CD28 - 穿孔素 +）表型的T细胞克隆扩增，已知该表型与更长的生存期相关，并推测可识别肿瘤表位，该分析表明这些克隆不太可能仅针对肿瘤免疫球蛋白，并提示有必要扩大搜索范围，寻找能够在体内刺激细胞毒性T细胞的肿瘤表位。
