Analysis of the association of peptides of optimal length to class I molecules on the surface of cells.
Analysis of the association of peptides of optimal length to class I molecules on the surface of cells.
复制标题
分析最佳长度的肽与细胞表面 I 类分子的关联。
DOI：
10.1073/pnas.89.19.8918
复制
发表时间：
1992
影响因子：
11.1
通讯作者：
Benacerraf,B
中科院分区：
文献类型：
--
作者：
Rock,KL;Rothstein,L;Benacerraf,B
研究了细胞表面的主要组织相容性复合体（MHC） I类分子与合成的含有8或9个氨基酸残基的抗原肽的关联。合成的多肽对应于卵清蛋白和流感核蛋白的抗原序列，这些序列被认为分别由具有Kb和Db MHC I类分子的细胞自然加工和呈递。与其他人的结果一致，这些肽在刺激特定T细胞方面的活性是较长序列肽的10(3)-10(5)倍。当细胞与这些肽在小于0.01-0.1微米的温度下孵育时，肽与I类分子的结合依赖于(I)来自细胞外液的游离β 2-微球蛋白的重新结合，（ii）一个需要细胞代谢活跃的过程，或（iii）通过化学交联稳定I类异源二聚体。相反，当细胞与这些肽在大于0.1-1.0微米的温度下孵育时，肽在缺乏外源性β 2-微球蛋白、能量或化学交联的情况下与I类分子结合。抗原竞争实验表明，结合高浓度肽的I类分子只会短暂接受结合肽。在这些条件下，呈递给T细胞所需的肽浓度对应于在缺乏外源性β 2微球蛋白的情况下，在RMA-S突变细胞表面稳定Kb分子的肽浓度。这些结果支持了一类分子在细胞上的接受性是由缺乏结合肽的MHC一类中β 2-微球蛋白的解离决定的。
The association of major histocompatibility complex (MHC) class I molecules on the surface of cells with synthetic antigenic peptides of eight or nine amino acid residues was examined. Peptides were synthesized that correspond to the antigenic sequences from ovalbumin and influenza nucleoprotein believed to be naturally processed and presented by cells with Kb and Db MHC class I molecules, respectively. Consistent with the results of others, these peptides were 10(3)-10(5) times more active in stimulating specific T cells as compared to peptides of longer sequences. When cells are incubated with these peptides at less than 0.01-0.1 microM, the association of the peptides with class I molecules is dependent on (i) the reassociation of free beta 2-microglobulin from the extracellular fluids, (ii) a process that requires cells to be metabolically active, or (iii) stabilization of class I heterodimers by chemical crosslinking. In contrast, when cells are incubated with these peptides at greater than 0.1-1.0 microM, the peptides associate with class I molecules in the absence of exogenous beta 2-microglobulin, energy, or chemical crosslinking. Antigen competition experiments suggest that the class I molecules that bind peptides offered at high concentration become only transiently receptive to binding peptide. The concentration of peptides required for presentation to T cells under these conditions corresponds to those that stabilize Kb molecules on the surface of RMA-S mutant cells in the absence of exogenous beta 2-microglobulin. These results support the concept that the receptivity of class I molecules on cells is determined by the dissociation of beta 2-microglobulin from MHC class I that lacks bound peptides.