期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 5, 页码 1505-1510出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1416543112
关键词
antigen presentation; peptide binding; anchor residues; dynamics; entropy
资金
- European Synchrotron Radiation Facility
- Swiss Light Source
- EMBO Long-Term Fellowship [ALTF_230-2010]
- Netherlands Organisation for Scientific Research (NWO) [722.011.011]
- NWO-TOP [91213078]
- Gravity Program Institute for Chemical Immunology
MHC class I molecules present a variable but limited repertoire of antigenic peptides for T-cell recognition. Understanding how peptide selection is achieved requires mechanistic insights into the interactions between the MHC I and candidate peptides. We find that, at first encounter, MHC I H-2K(b) considers a wide range of peptides, including those with expanded N termini and unfitting anchor residues. Discrimination occurs in the second step, when noncanonical peptides dissociate with faster exchange rates. This second step exhibits remarkable temperature sensitivity, as illustrated by numerous noncanonical peptides presented by H-2K(b) in cells cultured at 26 degrees C relative to 37 degrees C. Crystallographic analyses of H-2K(b)-peptide complexes suggest that a conformational adaptation of H-2K(b) drives the decisive step in peptide selection. We propose that MHC class I molecules consider initially a large peptide pool, subsequently refined by a temperature-sensitive induced-fit mechanism to retain the canonical peptide repertoire.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据