Anderson K S, Alexander J, Wei M, Cresswell P
Section of Immunobiology, Howard Hughes Medical Institute, Yale University Medical School, New Haven, CT 06510.
J Immunol. 1993 Oct 1;151(7):3407-19.
Intracellular transport and stability of class I MHC glycoproteins depends on the assembly of H chain, beta 2-microglobulin, and peptide. The Ag processing mutant cell lines T2 and RMA-S have defects in peptide loading of class I, resulting in reduced cell surface expression of class I molecules. Expression of class I molecules in the murine cell line RMA-S can be induced at 26 degrees C, suggesting that they are transported to the cell surface, but are unstable. However, most human class I molecules in T2 are poorly expressed at the cell surface, even at 26 degrees C. To directly compare the transport of human and mouse alleles in RMA-S and T2, the human alleles HLA-A2, A3, and B27 were transfected into RMA-S along with human beta 2-microglobulin, and the mouse alleles H-2Kb and Db were transfected into T2. Surface expression of HLA-A3 and B27 in RMA-S remained less than 10% of wild-type levels at 26 degrees C. H-2Kb and Db in both cell lines, however, were expressed at 20 to 30% wild-type levels at 37 degrees C and could be induced to wild-type levels at 26 degrees C or with peptides. The selective expression of murine class I glycoproteins at the cell surface of T2 is not because of their greater stability when associated with human beta 2m, since H-2Kb and Db H chain/human beta 2m complexes dissociate more rapidly in vitro than HLA-A3 and B27 complexes. These results suggest that the difference in transport between human and mouse class I in T2 reflects a fundamental structural property of the class I glycoproteins.
I类主要组织相容性复合体（MHC）糖蛋白的细胞内运输和稳定性取决于重链、β2-微球蛋白和肽的组装。抗原加工突变细胞系T2和RMA-S在I类肽负载方面存在缺陷，导致I类分子在细胞表面的表达减少。鼠细胞系RMA-S中I类分子的表达在26℃时可被诱导，这表明它们被转运到细胞表面，但不稳定。然而，T2中的大多数人类I类分子即使在26℃时在细胞表面的表达也很差。为了直接比较RMA-S和T2中人类和小鼠等位基因的运输情况，将人类等位基因HLA-A2、A3和B27与人β2-微球蛋白一起转染到RMA-S中，将小鼠等位基因H-2Kb和Db转染到T2中。在26℃时，RMA-S中HLA-A3和B27的表面表达仍低于野生型水平的10%。然而，两个细胞系中的H-2Kb和Db在37℃时以野生型水平的20%至30%表达，并且在26℃或用肽处理时可被诱导至野生型水平。T2细胞表面鼠I类糖蛋白的选择性表达并不是因为它们与人β2m结合时具有更高的稳定性，因为H-2Kb和Db重链/人β2m复合物在体外比HLA-A3和B27复合物解离得更快。这些结果表明，T2中人类和小鼠I类在运输上的差异反映了I类糖蛋白的一种基本结构特性。
