免疫系统的特征是可以辨别自体和异体。细胞毒性T淋巴细胞（CTL）可透过其细胞表面的受体（TCR），检查在所有人体细胞表面表现的MHC I类复合体的身份标记。
假如细胞受到病毒、细菌或寄生虫侵入，或发生癌变，来自入侵者的蛋白碎片会装载到MHC I类分子上形成肽复合体（p—MHC），T细胞将识别该变化，并杀死携带有病原体的宿主细胞或癌变细胞。
根据一篇发表于2007年4月6日Cell中的文章，斯坦福大学医学院、霍华德休斯医学院和伊利诺斯州大学的研究人员，在论文中描述了T细胞受体如何识别自己和外源的主要组织兼容性复合体(major histocompatibility complex,MHC)。MHC是脊椎动物体内，与免疫反应调节有关的一个基因家族。
αβT细胞受体（TCRs）能够与自己的和外来的MHC蛋白交互作用，这就是所谓的同种排斥反应，也就是T细胞对同种异体组织发生免疫反应。在这篇论文中，研究人员提出了2C TCR与它的外源配基H-2Ld-Q配体的结构。研究人员惊讶地发现，这种TCR利用一种不同寻常的策略，使用外源的pMHC。
(资料来源 : biocompare)
部分英文原文:
Cell, Vol 129, 135-146, 06 April 2007
Article
How a Single T Cell Receptor Recognizes Both Self and Foreign MHC
Leremy A. Colf,1,3 Alexander J. Bankovich,1,3 Nicole A. Hanick,1 Natalie A. Bowerman,2 Lindsay L. Jones,2 David M. Kranz,2 and K. Christopher Garcia1,
1 Howard Hughes Medical Institute, Departments of Molecular and Cellular Physiology, and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
2 Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Corresponding author
K. Christopher Garcia
kcgarcia@stanford.edu
αβ T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 Å structure of the 2C TCR complexed with its foreign ligand H-2Ld-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2Kb-dEV8. 2C engages both shared and polymorphic residues on Ld and Kb, as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the Ld-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2Ld-QL9, the “wild-type” TCR-MHC binding orientation persists despite modified TCR-CDR3α interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.
英文全文链接：http://www.cell.com/content/article/fulltext?uid=PIIS0092867407003133
上一篇：女性可制造精子自行受孕 未来女同性恋生育将成可能 下一篇：JCI：葡萄糖引起低血糖昏迷的大鼠脑细胞死亡
|
