Archbold Julia K, Ely Lauren K, Kjer-Nielsen Lars, Burrows Scott R, Rossjohn Jamie, McCluskey James, Macdonald Whitney A
The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
Mol Immunol. 2008 Feb;45(3):583-98. doi: 10.1016/j.molimm.2006.05.018. Epub 2007 Sep 14.
A great paradox in cellular immunology is how T cell allorecognition exists at high frequencies (up to 10%) despite the stringent requirements of discriminating 'self' from 'non-self' imposed by MHC restriction. Thus, in tissue transplantation, a substantial proportion of the recipient's T cells will have the ability to recognize the graft and instigate an immune response against the transplanted tissue, ultimately resulting in graft rejection--a manifestation of T cell alloreactivity. Transplantation of human organs and lymphoid cells as treatment for otherwise life-threatening diseases has become a more routine medical procedure making this problem of great importance. Immunologists have gained important insights into the mechanisms of T cell alloreactivity from cytotoxic T cell assays, affinity-avidity studies, and crystal structures of peptide-MHC (pMHC) molecules and T cell receptors (TCRs) both alone and in complex. Despite the clinical significance of alloreactivity, the crystal structure of an alloreactive human TCR in complex with both cognate pMHC and an allogeneic pMHC complex has yet to be determined. This review highlights some of the important findings from studies characterizing the way in which alloreactive T cell receptors and pMHC molecules interact in an attempt to resolve this great irony of the cellular immune response.
细胞免疫学中的一个重大悖论是，尽管主要组织相容性复合体（MHC）限制对区分“自身”和“非自身”有严格要求，但T细胞同种异体识别却以高频率存在（高达10%）。因此，在组织移植中，受体的相当一部分T细胞将有能力识别移植物并引发针对移植组织的免疫反应，最终导致移植物排斥——这是T细胞同种异体反应性的一种表现。作为治疗其他危及生命疾病的手段，人类器官和淋巴细胞移植已成为一种更为常规的医疗程序，这使得这个问题变得极为重要。免疫学家通过细胞毒性T细胞检测、亲和力-亲合力研究以及单独和复合状态下的肽-MHC（pMHC）分子和T细胞受体（TCR）的晶体结构，对T细胞同种异体反应性的机制有了重要认识。尽管同种异体反应性具有临床意义，但与同源pMHC和同种异体pMHC复合物复合的同种异体反应性人类TCR的晶体结构尚未确定。本综述重点介绍了一些研究的重要发现，这些研究描述了同种异体反应性T细胞受体与pMHC分子相互作用的方式，试图解决细胞免疫反应中的这一重大矛盾。
