The Amino Acid Sequences Flanking an Antigenic Determinant Can Strongly Affect MHC Class I Cross-Presentation without Altering Direct Presentation
The Amino Acid Sequences Flanking an Antigenic Determinant Can Strongly Affect MHC Class I Cross-Presentation without Altering Direct Presentation
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DOI：
10.4049/jimmunol.0803806
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发表时间：
2009-04-15
影响因子：
4.4
通讯作者：
Sigal, Luis J.
中科院分区：
文献类型：
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作者：
Ma, Xueying;Serna, Amparo;Sigal, Luis J.
专业APC在MHC I上的直接呈递(DP)和交叉呈递(CP)分别由Ag的内部或外部来源定义。虽然有些AGS是DP和CP的底物，但其他AGS只是DIP的底物。造成这种差异的原因在很大程度上仍不清楚。在这项研究中，我们在组织培养和体内研究了改变MHC I类限制性决定簇(鸡OVA OVA(258-265)，SIINFEKL)两侧氨基酸链的长度和序列的影响，该决定簇通常是DP和CP的良好底物。我们证明了CP而不是DP严格地要求侧翼N和C-末端扩展的最小长度。此外，我们表明，仅移除但不是替换决定簇下游的一个氨基酸22残基就足以强烈影响CP而不影响蛋白质的稳定性或DP。因此，我们的工作表明，抗原决定簇的侧翼残基可以不同地影响CP和DP，而抗原的特性而不是半衰期可以对CP产生重大影响。我们的研究可能会对理解CP在病毒感染中的作用，并可能对新疫苗的设计产生影响。免疫学杂志，2009,182：4601-4607。
Direct presentation (DP) and cross presentation (CP) on MHC I by professional APCs are defined by the internal or external source of the Ag, respectively. Although some Ags are substrates for both DP and CP, others are only substrates for DIP. The reasons for this difference remain largely unknown. In this study, we studied in tissue culture and also in vivo, the effects of altering the length and sequence of the amino acid chains flanking an MHC class I restricted determinant (the chicken OVA OVA(258-265), SIINFEKL) that is normally a good substrate for both DP and CP. We demonstrate that CP but not DP strictly requires flanking N and C-terminal extensions of minimal length. Furthermore, we show that removal but not replacement of just one amino acid 22 residues downstream from the determinant is sufficient to strongly affect CP without affecting either protein stability or DP. Thus, our work shows that the flanking residues of an antigenic determinant can differentially affect CP and DP, and that features of the Ag other than half-life can have a major impact in CP. Our studies may have implications for understanding CP in viral infections and possibly for the design of new vaccines. The Journal of Immunology, 2009, 182: 4601-4607.