Structural features of the acyl chain determine self-phospholipid antigen recognition by a CD1d-restricted invariant NKT (iNKT) cell
Structural features of the acyl chain determine self-phospholipid antigen recognition by a CD1d-restricted invariant NKT (iNKT) cell
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DOI：
10.1074/jbc.m308089200
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发表时间：
2003-11-28
影响因子：
4.8
通讯作者：
Behar, SM
中科院分区：
文献类型：
--
作者：
Rauch, J;Gumperz, J;Behar, SM
目前对CD 1d限制性T细胞的抗原特异性知之甚少，只知道它们在缺乏外源性抗原的情况下经常识别表达CD 1d的抗原呈递细胞。我们之前证明了24.8.A iNKT细胞杂交瘤与CD 1d转染的细胞系具有广泛反应性，并识别肿瘤细胞提取物的极性脂质部分。在本研究中，将24.8.A iNKT细胞杂交瘤识别的抗原纯化至均一，并鉴定为棕榈酰-油酰-sn-甘油基-3-磷酸乙醇胺（16：0 - 18：1 PE）。24.8 iNKT细胞杂交瘤识别合成的16：0-18：1[顺式] PE，证实该磷脂具有抗原性。识别与酰基链的不饱和度相关。使用一组合成PE，24.8. iNKT细胞杂交瘤显示被含有至少一个不饱和酰基链的PE激活。双键的构型很重要，如24.8。iNKT细胞杂交瘤识别顺式而非反式构型的不饱和酰基链。具有多个双键的PE比具有单个双键的PE被更好地识别，并且增加的酰基链不饱和度与PE与CD 1d的结合增加相关。这些数据说明了磷脂抗原结合CD 1d的酰基链结构的潜在重要性。
Little is known about the antigen specificity of CD1d-restricted T cells, except that they frequently recognize CD1d-expressing antigen-presenting cells in the absence of exogenous antigen. We previously demonstrated that the 24.8.A iNKT cell hybridoma was broadly reactive with CD1d-transfected cell lines and recognized the polar lipid fraction of a tumor cell extract. In the present study, the antigen recognized by the 24.8.A iNKT cell hybridoma was purified to homogeneity and identified as palmitoyl-oleoyl-sn-glycero-3-phosphoethanolamine (16: 0 - 18: 1 PE). The 24.8. A iNKT cell hybridoma recognized synthetic 16: 0-18: 1[cis] PE, confirming that this phospholipid is antigenic. Recognition correlated with the degree of unsaturation of the acyl chains. Using a panel of synthetic PEs, the 24.8. A iNKT cell hybridoma was shown to be activated by PEs that contained at least one unsaturated acyl chain. The configuration of the double bonds was important, as the 24.8. A iNKT cell hybridoma recognized unsaturated acyl chains in the cis, but not the trans, configuration. PEs with multiple double bonds were recognized better than those with a single double bond, and increasing acyl chain unsaturation correlated with increased binding of PE to CD1d. These data illustrate the potential importance of the acyl chain structure for phospholipid antigen binding to CD1d.