Saini Sunil Kumar, Schuster Heiko, Ramnarayan Venkat Raman, Rammensee Hans-Georg, Stevanović Stefan, Springer Sebastian
Molecular Life Science, Jacobs University Bremen, 28759 Bremen, Germany; and.
Department of Immunology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):202-7. doi: 10.1073/pnas.1418690112. Epub 2014 Dec 22.
Peptide ligand selection by MHC class I molecules, which occurs by iterative optimization, is the centerpiece of immunodominance in antiviral and antitumor immune responses. For its understanding, the molecular mechanisms of peptide binding and dissociation by class I molecules must be elucidated. To this end, we have investigated dipeptides that bind to the F pocket of class I molecules. We find that they accelerate the dissociation of prebound peptides of both low and high affinity, suggesting a mechanism of action for the peptide-exchange chaperone tapasin. Peptide exchange on class I molecules also has practical uses in epitope discovery and T-cell monitoring.
通过迭代优化进行的MHC I类分子肽配体选择，是抗病毒和抗肿瘤免疫反应中免疫优势的核心。为了理解这一过程，必须阐明I类分子肽结合和解离的分子机制。为此，我们研究了与I类分子F口袋结合的二肽。我们发现它们加速了低亲和力和高亲和力预结合肽的解离，提示了肽交换伴侣蛋白塔帕辛的作用机制。I类分子上的肽交换在表位发现和T细胞监测中也有实际应用。
