Cutting edge: TCR contacts as anchors: effects on affinity and HLA-DM stability. J Immunol 2003 Dec 01;171(11):5683-7
Date
11/25/2003Pubmed ID
14634075DOI
10.4049/jimmunol.171.11.5683Scopus ID
2-s2.0-0345016487 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
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-binding 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.
Author List
Anderson MW, Gorski JAuthor
Matthew W. Anderson MD, PhD Assistant Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SubstitutionAnimals
Antigen Presentation
Binding, Competitive
Cell Line
Drosophila
Epitopes, T-Lymphocyte
HLA-D Antigens
HLA-DR1 Antigen
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Hydrophobic and Hydrophilic Interactions
Influenza A virus
Peptide Fragments
Protein Binding
Receptors, Antigen, T-Cell