Presentation of a determinant by MHC class II can be prevented through competitive capture by a flanking determinant on a multideterminant peptide.
Presentation of a determinant by MHC class II can be prevented through competitive capture by a flanking determinant on a multideterminant peptide.
复制标题
通过多决定簇肽上的侧翼决定簇的竞争性捕获，可以防止 II 类 MHC 呈递决定簇。
DOI：
10.1016/j.jaut.2008.02.004
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发表时间：
2008
影响因子：
12.8
通讯作者：
Sercarz,EliE
中科院分区：
文献类型：
--
作者：
Maverakis,Emanual;Beech,JonathanT;Schneider,Susanne;Sercarz,EliE
竞争性捕获是一个过程，通过该过程，解折叠抗原的不同决定簇竞争结合相同的MHC II类分子。“胜利”的决定因素，然后占主导地位的显示。对于自身抗原，对显性展示的决定簇具有特异性的T细胞将经受强耐受诱导。考虑到这一点，我们开始描述的Golli MBP复杂的交界区的行列式层次结构。在该区域内，已知MBP 1-9决定簇是实验性自身免疫性脑脊髓炎的强诱导物。我们发现，Golli-MBP连接区包含三个重叠的决定因素：LDVM 1 -5，MBP 1-9，和MBP 7-20的三联体。我们表明，这三个决定因素是独特的，竞争结合I-Au和一个决定因素的层次结构存在与MBP 7-20是最主要的显示决定因素。由于阻止了MBP 1 -9与MHC-II的接触，因此该决定子的剩余T细胞库保持完整，从而允许其最高亲和力的成员驱动应答，并将MBP 1 -9转化为显性决定子，尽管其MHC结合能力较差。
Competitive capture is a process by which different determinants of an unfolding antigen compete for binding to the same MHC class II molecule. The “winning” determinant is then dominantly displayed. For self antigens, T cells with specificity for dominantly displayed determinants will be subject to strong tolerance induction. With this in mind we set out to characterize the determinant hierarchy of the junctional region of the Golli-MBP complex. Within this region the MBP 1–9 determinant is known to be a strong inducer of experimental autoimmune encephalomyelitis. We found that the Golli-MBP junctional region contains a triad of three overlapping determinants: LDVM1–5, MBP 1–9, and MBP 7–20. We demonstrate that these three determinants are unique and compete for binding to I-Auand that a determinant hierarchy exists with MBP 7–20 being the most dominantly displayed determinant. Because of the prevention of MBP1–9 access to MHC-II, the residual T cell repertoire to this determinant remains complete, thereby permitting its highest affinity members to drive the response, and to convert MBP1–9 into a dominant determinant, despite its poor MHC binding capacity.