Computational Alanine Scanning Reveals Common Features of TCR/pMHC Recognition in HLA-DQ8-Associated Celiac Disease

Linqiong Qiu, Jianing Song, John Z.H. Zhang

Research output: Chapter in Book/Report/Conference proceedingChapter


In HLA-DQ8-associated celiac disease, Gliadin-γ1 or Gliadin-α1 peptide is presented to the cell surface and recognized by several types of T-cell receptor (TCR), but it is still unclear how the TCR, peptide, and the major histocompatibility complex (MHC) act together to trigger celiac disease. For now, most of the analysis is based on static crystal structures. And the detailed information about these structures based on energetic interaction is still lacking. Here, we took four types of celiac disease-related MHC-peptide-TCR structures from three patients to perform computational alanine scanning calculations using the molecular mechanics generalized born surface area (MM/GBSA) approach combined with a recently developed interaction entropy (IE) method to identify the key residues on TCR, peptide, and MHC. Our study aims to shed some light on the interaction mechanism of this complex protein interaction system. Based on detailed computational analysis and mutational calculations, important binding interactions in these triple-interaction complexes are analyzed, and critical residues responsible for TCR/pMHC recognition pattern in HLA-DQ8-associated celiac disease are presented. These detailed analysis and computational result should help shed light on our understanding of the celiac disease and the development of the medical treatment.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Number of pages20
StatePublished - 2022

Publication series

NameMethods in Molecular Biology
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029


  • Binding affinity
  • Celiac disease
  • GBSA
  • HLA-DQ8
  • Interaction entropy
  • MHC
  • Peptide
  • Protein–protein
  • TCR
  • Alanine
  • Receptors, Antigen, T-Cell/genetics
  • Humans
  • Models, Molecular
  • Histocompatibility Antigens
  • Peptides/metabolism
  • HLA-DQ Antigens
  • Gliadin
  • Celiac Disease
  • Protein Binding

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology


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