Kozlowski S, Takeshita T, Boehncke W H, Takahashi H, Boyd L F, Germain R N, Berzofsky J A, Margulies D H
Molecular Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Nature. 1991 Jan 3;349(6304):74-7. doi: 10.1038/349074a0.
T lymphocytes expressing alpha beta receptors recognize antigenic peptide fragments bound to major histocompatibility complex class I or class II molecules present on the surface membranes of other cells. Peptide fragments are present in the two available HLA crystal structures and recent data indicate that peptide is required for the stable folding of the class I heavy chain and maintenance of its association with the class I light chain, beta 2-microglobulin (beta 2m), at physiological temperature. To explain how the exogenous peptide used to create targets for cytotoxic cells bearing CD8 antigen could associate with apparently peptide-filled extracellular class I molecules, we hypothesized that stable binding of exogenous peptide to mature class I molecules reflects either the replacement of previously bound peptide during the well documented beta 2m exchange process or the loading of 'empty' class I heavy chains dependent on the availability of excess beta 2m. In either case, free beta 2m should enhance peptide/class I binding. Using either isolated soluble class I molecules or living cells, we show here that free purified beta 2m markedly augments the generation of antigenic complexes capable of T-cell stimulation.
表达αβ受体的T淋巴细胞识别与其他细胞表面膜上存在的主要组织相容性复合体I类或II类分子结合的抗原肽片段。肽片段存在于两种可用的HLA晶体结构中，最近的数据表明，在生理温度下，肽对于I类重链的稳定折叠及其与I类轻链β2-微球蛋白（β2m）的结合维持是必需的。为了解释用于为携带CD8抗原的细胞毒性细胞创建靶标的外源性肽如何与明显充满肽的细胞外I类分子结合，我们假设外源性肽与成熟I类分子的稳定结合反映了在充分记录的β2m交换过程中先前结合的肽的替换，或者是依赖于过量β2m可用性的“空”I类重链的加载。在任何一种情况下，游离的β2m都应增强肽/I类的结合。在这里，我们使用分离的可溶性I类分子或活细胞表明，游离的纯化β2m显著增强了能够刺激T细胞的抗原复合物的产生。
