Altered TCR ligands affect antigen-presenting cell responses: up-regulation of IL-12 by an analogue peptide.
Altered TCR ligands affect antigen-presenting cell responses: up-regulation of IL-12 by an analogue peptide.
复制标题
改变的 TCR 配体影响抗原呈递细胞反应：类似肽上调 IL-12。
作者：
T. Matsuoka;H. Kohrogi;M. Ando;Y. Nishimura;S. Matsushita
当检查类似肽对识别肽片段的人Th 0克隆DT 13.2的应答模式变化的影响时（18 RSLRTVTPIRMQGG 31）在HLA-DQ 6背景下源自粉尘螨中的I组变应原（DQA 1 *0102/DQB 1 *0602），我们发现第21位残基Arg替换为Lys导致IFN-γ产生的显著增加，在高剂量的肽下，增殖反应或IL-4产生没有显著变化。通过类似物肽选择性增强IFN-γ产生伴随着IL-12产生的增加，其被抗IL-12 Ab抑制至野生型肽诱导的IFN-γ产生水平。相反，与IFN-γ和IFN-γ受体的中和Ab共孵育不影响IL-12的产生，表明由类似物肽刺激的IL-12的产生增加不是由于来自T细胞的IFN-γ的作用。在高肽浓度下肽诱导的CD 40配体表达上调显示野生型和类似肽之间没有差异。这些数据共同表明，某些T细胞/APC的相互作用介导的TCR和改变TCR配体影响APC的反应，并传递到APC的信号是不可或缺的那些T细胞在确定T细胞的反应模式。
When examining the effects of analogue peptides on changes in response patterns of a human Th0 clone DT13.2 that recognizes a peptide fragment (18RSLRTVTPIRMQGG31) derived from a group I allergen in Dermatophagoides farinae in the context of HLA-DQ6 (DQA1*0102/DQB1*0602), we found that replacement of the 21st residue Arg to Lys resulted in a significant increase in IFN-gamma production, with no remarkable changes either in proliferative response or IL-4 production, at high doses of the peptide. Selective enhancement of IFN-gamma production by the analogue peptide was accompanied by an increased production of IL-12, which was suppressed by an anti-IL-12 Ab down to the level of IFN-gamma production induced by the wild-type peptide. On the contrary, co-incubation with neutralizing Abs to IFN-gamma and IFN-gamma receptor did not affect IL-12 production, indicating that increased production of IL-12 stimulated by the analogue peptide was not due to an effect of IFN-gamma from T cells. Peptide-induced up-regulation of CD40 ligand expression at high peptide concentrations showed no difference between the wild-type and analogue peptides. These data collectively indicate that certain T cell/APC interactions mediated through TCR and altered TCR ligands affect APC responses and that signals transmitted to APC are as indispensable as those to T cells in determining T cell response patterns.