Characterization of T cell hybridomas raised against a glycopeptide containing the tumor-associated T antigen, (βGal (1-3) αGalNAc-O/Ser)
Characterization of T cell hybridomas raised against a glycopeptide containing the tumor-associated T antigen, (βGal (1-3) αGalNAc-O/Ser)
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DOI：
10.1023/a:1022537031617
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发表时间：
2002-01-01
影响因子：
3
通讯作者：
Jensen, T
中科院分区：
文献类型：
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作者：
Gad, M;Werdelin, O;Jensen, T
T 细胞杂交瘤针对糖肽 S-72 (Core-1) 进行培养，该糖肽 S-72 (Core-1) 含有肿瘤相关二糖 betaGal (1-3) alphaGalNAc (Core-1)，与小鼠血红蛋白衍生的十肽 Hb(67-76) 中第 72 位的丝氨酸 O 连接。所有杂交瘤均识别糖肽 S-72 (Core-1)。然而，两个选定的杂交瘤对含有丝氨酸连接的单糖 aGalNAc O 的 S-72 (Tn) 糖肽的反应要好得多。此外，一种杂交瘤与第72位具有苏氨酸而不是丝氨酸的糖肽T-72（Core-1）发生交叉反应。未发现与由连接有不同聚糖的相同血红蛋白肽或未糖基化肽组成的其他糖肽存在交叉反应。 T 细胞受体 Valpha 和 Vbeta 的使用明显不同。此外，CDR3α区域显示出小极性氨基酸侧链的优势，并且三个杂交瘤包含共同的序列基序。所有测序的 CDR3β 区域还包含保守的脯氨酸-甘氨酸基序。总之，用含有二糖的糖肽 S-72 (Core-1) 进行免疫产生了糖肽特异性 T 细胞的异质群体，具有对相关糖肽交叉反应的能力。
T cell hybridomas were raised against the glycopeptide S-72 (Core-1) containing the tumor-associated disaccharide betaGal (1-3) alphaGalNAc (Core-1) O-linked to serine at position 72 in the mouse hemoglobin derived decapeptide Hb(67-76). All hybridomas recognized the glycopeptide S-72 (Core-1). Two of the selected hybridomas responded, however, much better to the S-72 (Tn) glycopeptide containing the monosaccharide aGalNAc O-linked to serine. In addition, one hybridoma cross-responded to the glycopeptide T-72 (Core-1) having a threonine at position 72 instead of a serine. No cross-responses were found to other glycopeptides consisting of the same hemoglobin peptide with different glycans attached or to the unglycosylated peptides. The T cell receptor Valpha and Vbeta usage was clearly diverse. The CDR3alpha regions demonstrated moreover a predominance of small polar amino acid side chains, and three hybridomas contained a common sequence motif. All the sequenced CDR3beta regions contained furthermore a conserved proline-glycine motif. In conclusion, immunization with the disaccharide containing glycopeptides S-72 (Core-1) created a heterogeneous population of glycopeptide specific T cells with the ability of cross-responding toward related glycopeptides.