Berwin B, Rosser M F N, Brinker K G, Nicchitta C V
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Traffic. 2002 May;3(5):358-66. doi: 10.1034/j.1600-0854.2002.30505.x.
GRP94 (gp96)-associated peptides can elicit cellular immune responses, an activity thought to reflect the presence of a cell surface receptor (CD91) on antigen-presenting cells that mediates GRP94 internalization and trafficking to an amenable site for peptide transfer to major histocompatibility complex class I molecules. We report that GRP94 internalized by receptor-mediated endocytosis is trafficked to a Rab5a, CD1 and transferrin-negative, Fc receptor and major histocompatibility complex class I-positive endocytic compartment. Receptor-internalized GRP94 did not access the endoplasmic reticulum of antigen-presenting cells. To identify the site of re-presentation of GRP94-associated peptides, kinetic analyses were performed utilizing GRP94-OVA (SIINFEKL) peptide complexes, with peptide re-presentation assayed with the Kb-SIINFEKL-specific MAb, 25-D1.16. Analyses of the kinetics of re-presentation of GRP94-associated peptides, under conditions in which de novo synthesis of major histocompatibility complex class I molecules was inhibited, identified a post-endoplasmic reticulum compartment, accessed by mature major histocompatibility complex class I, as the predominant site of GRP94-associated peptide exchange onto major histocompatibility complex class I.
GRP94（gp96）相关肽可引发细胞免疫反应，这种活性被认为反映了抗原呈递细胞上存在一种细胞表面受体（CD91），该受体介导GRP94内化并转运至一个适宜的位点，以便将肽转移至主要组织相容性复合体I类分子。我们报告称，通过受体介导的内吞作用内化的GRP94被转运至一个Rab5a、CD1和转铁蛋白阴性、Fc受体和主要组织相容性复合体I类阳性的内吞区室。受体内化的GRP94未进入抗原呈递细胞的内质网。为了确定GRP94相关肽重新呈递的位点，利用GRP94-OVA（SIINFEKL）肽复合物进行了动力学分析，并用Kb-SIINFEKL特异性单克隆抗体25-D1.16检测肽的重新呈递。在主要组织相容性复合体I类分子的从头合成受到抑制的条件下，对GRP94相关肽重新呈递的动力学分析确定了一个内质网后区室，成熟的主要组织相容性复合体I类可进入该区域，这是GRP94相关肽交换至主要组织相容性复合体I类上的主要位点。
