Cutting edge: TCR contacts as anchors: Effects on affinity and HLA-DM stability

被引:17
作者
Anderson, MW
Gorski, J
机构
[1] Ctr Blood SE Wisconsin, Blood Res Inst, Milwaukee, WI 53201 USA
[2] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53201 USA
关键词
D O I
10.4049/jimmunol.171.11.5683
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Peptides presented via the class II MHC (MHCII) pathway are selected based on affinity for MHCII and stability in the presence of HLA-DM. Currently, epitope selection is thought to be controlled by the ability of peptide to sequester "anchor" residues into pockets in the MHCII Residues exhibiting higher levels of solvent accessibility have been shown to contact TCR, but their roles in affinity and complex stability have not been directly studied. Using the HLA-DR1-hinding influenza peptide, hemagglutinin (306-318), as a model, we show that side chain substitutions at these positions influence affinity and HLA-DM stability. Multiple substitutions reduce affinity to a greater extent than the loss of the major P1 anchor residue. We propose that these effects may be mediated through the H-bond network. These results demonstrate the importance of solvent-exposed residues in epitope selection and blur the distinctions between anchor and TCR contact residues.
引用
收藏
页码:5683 / 5687
页数:5
相关论文
共 32 条
[31]   Human histocompatibility leukocyte antigen (HLA)-DM edits peptides presented by HLA-DR according to their ligand binding motifs [J].
vanHam, SM ;
Gruneberg, U ;
Malcherek, G ;
Broker, I ;
Melms, A ;
Trowsdale, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (05) :2019-2024
[32]   Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM [J].
Weber, DA ;
Evavold, BD ;
Jensen, PE .
SCIENCE, 1996, 274 (5287) :618-620