Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Immunol Cell Biol. 2010 Jan;88(1):57-62. doi: 10.1038/icb.2009.59. Epub 2009 Aug 18.
Major histocompatibility complex (MHC) class I heavy chain/beta(2)m heterodimers assemble with antigenic peptides through interactions with peptide-loading complex proteins, including tapasin and ERp57. In human cells, a cysteine residue within tapasin (C95) has been shown to form a covalent bond with ERp57. In this study, we focused on the effect of this tapasin amino-acid residue in mouse cells expressing the MHC class I molecule H2-K(d). We showed that a large disulfide-bonded complex was present in the mouse cells that included ERp57, tapasin, and K(d). Furthermore, in mouse cells, unlike human cells, we found that tapasin mutated at C95 can participate in a non-covalent complex with ERp57. Comparison of our findings to earlier findings with a human molecule (HLA-B()4402) also revealed that a tapasin C95 mutation has a stronger effect on the maturation and stability of K(d) than HLA-B()4402. Overall, our results characterize the influence of this tapasin cysteine residue on the stable surface expression of a mouse MHC class I molecule and reveal differences in tapasin C95 interactions and effects between mouse and human systems.
主要组织相容性复合体（MHC）I 类重链/β2m 异二聚体通过与肽加载复合物蛋白（包括 tapasin 和 ERp57）的相互作用与抗原肽组装。在人类细胞中，tapasin（C95）内的一个半胱氨酸残基已被证明与 ERp57 形成共价键。在这项研究中，我们专注于在表达 MHC I 类分子 H2-K(d)的小鼠细胞中该 tapasin 氨基酸残基的作用。我们表明，在包括 ERp57、tapasin 和 K(d)的小鼠细胞中存在一个大的二硫键结合复合物。此外，与人类细胞不同，我们发现 C95 突变的 tapasin 可以与 ERp57 形成非共价复合物。将我们的发现与之前对人类分子（HLA-B()4402）的发现进行比较还表明，tapasin C95 突变对 K(d)的成熟和稳定性的影响比对 HLA-B()4402 的影响更强。总的来说，我们的结果描述了该 tapasin 半胱氨酸残基对小鼠 MHC I 类分子稳定表面表达的影响，并揭示了 tapasin C95 相互作用和小鼠与人类系统之间的影响的差异。
