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The 3A6‐TCR/superagonist/HLA‐DR2a complex shows similar interface and reduced flexibility compared to the complex with self‐peptide
Author(s) -
Salutari Ilaria,
Martin Roland,
Caflisch Amedeo
Publication year - 2020
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25764
Subject(s) - t cell receptor , major histocompatibility complex , peptide , myelin basic protein , t cell , human leukocyte antigen , chemistry , peptide sequence , biology , microbiology and biotechnology , antigen , immune system , immunology , biochemistry , myelin , neuroscience , gene , central nervous system
T‐cell receptor (TCR) recognition of the myelin basic protein (MBP) peptide presented by major histocompatibility complex (MHC) protein HLA‐DR2a, one of the MHC class II alleles associated with multiple sclerosis, is highly variable. Interactions in the trimolecular complex between the TCR of the MBP83‐99‐specific T cell clone 3A6 with the MBP‐peptide/HLA‐DR2a (abbreviated TCR/pMHC) lead to substantially different proliferative responses when comparing the wild‐type decapeptide MBP90‐99 and a superagonist peptide, which differs mainly in the residues that point toward the TCR. Here, we investigate the influence of the peptide sequence on the interface and intrinsic plasticity of the TCR/pMHC trimolecular and pMHC bimolecular complexes by molecular dynamics simulations. The intermolecular contacts at the TCR/pMHC interface are similar for the complexes with the superagonist and the MBP self‐peptide. The orientation angle between TCR and pMHC fluctuates less in the complex with the superagonist peptide. Thus, the higher structural stability of the TCR/pMHC tripartite complex with the superagonist peptide, rather than a major difference in binding mode with respect to the self‐peptide, seems to be responsible for the stronger proliferative response.