Solheim J C
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805, USA.
Immunol Rev. 1999 Dec;172:11-9. doi: 10.1111/j.1600-065x.1999.tb01352.x.
Several years ago, the only factor known to be necessary for the assembly and surface expression of class I MHC was beta 2m; even for beta 2m, it was unclear at what point in class I maturation its role was played. Recent experiments that employed attachment of an endoplasmic reticulum (ER) retention signal to beta 2m have shown that the point of time at which beta 2m is required is while the class I heavy chain is in the ER. Later association between beta 2m and class I is not vital in order for properly folded class I to be expressed at the cell surface. After crystallization of the first class I MHC molecule, it was realized that not only is antigen presented by class I, but that antigen is presented in the form of a peptide that stabilizes the class I structure and allows its transit to the cell surface. Class I allelic differences influence interactions with both peptide and beta 2m, with likely consequences for the ability of the class I heavy chains to present antigen through alternative pathways. Furthermore, it is now also clear that formation of appropriate disulfide bonds in the class I heavy chain is needed before class I can bind peptide antigen securely, a process that may be assisted by an ER chaperone. Many different proteins that are resident in the ER, such as calnexin, transporter associated with antigen processing (TAP), calreticulin, and tapasin, have been found to be integral to class I assembly. TAP, tapasin, and calreticulin bind preferentially to the open form of class I, which can be distinguished with the use of a monoclonal antibody specific for this form. Calreticulin and calnexin contrast in their interactions with class I, despite other similarities between these two chaperones. Overall, class I MHC assembly is now understood to involve the interplay of multiple intra- and intermolecular events in a defined chronological order which ensure continual reporting of cellular contents to cytotoxic T lymphocytes.
几年前，已知对于I类主要组织相容性复合体（MHC）的组装和表面表达而言，唯一必需的因素是β2微球蛋白（β2m）；即便对于β2m，其在I类成熟过程中的作用时机仍不明确。最近的实验通过将内质网（ER）滞留信号连接到β2m上，结果表明β2m发挥作用的时间点是在I类重链位于内质网中时。β2m与I类随后的结合对于正确折叠的I类在细胞表面的表达并非至关重要。在首个I类MHC分子结晶后，人们认识到不仅I类能够呈递抗原，而且抗原是以一种肽的形式呈递的，这种肽可稳定I类结构并使其转运至细胞表面。I类等位基因差异会影响与肽和β2m的相互作用，这可能对I类重链通过替代途径呈递抗原的能力产生影响。此外，现在还清楚的是，在I类能够牢固结合肽抗原之前，I类重链中需要形成适当的二硫键，这一过程可能由内质网伴侣蛋白协助完成。已发现许多驻留在内质网中的不同蛋白质，如钙连蛋白、抗原加工相关转运体（TAP）、钙网蛋白和塔帕辛，对于I类组装不可或缺。TAP、塔帕辛和钙网蛋白优先结合I类的开放形式，可使用针对该形式的单克隆抗体进行区分。尽管这两种伴侣蛋白存在其他相似之处，但钙网蛋白和钙连蛋白与I类的相互作用有所不同。总体而言，现在认为I类MHC组装涉及多个分子内和分子间事件按特定时间顺序的相互作用，这些事件可确保持续向细胞毒性T淋巴细胞报告细胞内容物。
