Τίτλος:
Amino acid signatures in the HLA class II peptide-binding region associated with protection/susceptibility to the severe West Nile Virus disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The MHC class II region in humans is highly polymorphic. Each MHC molecule is formed by an α and a β chain, produced by different genes, creating an antigen-binding groove. In the groove there are several pockets into which antigens anchor and fit. The affinity of this fitting determines the recognition specificity of a given peptide. Here, based on our previous results about the association of MHC class II with the WNV disease, we examined the role of the binding pockets of HLA-DPA1, -DQA1 and-DRB1 in the severe form of the disease. In HLA-DQA1, variants in all pockets 1, 6 and 9 were found to be associated with either protection and/or susceptibility to neuroinvasion caused by WNV. Similarly, pockets 7, 9 and 10 in HLA-DRB1 were associated with severe disease. Protein modeling of these molecules revealed structural and functional differences among alleles with opposite roles concerning the development of the disease. Different amino acids in positions α52 and α66 (HLADQA1) significantly influenced the peptide binding while DYWLR/EFA combination (HLADRB1) was associated with neuronal damage. Further studies could help us understand the selectivity of pocket variants in order to create suitable peptides for an effective response. © 2018 Sarri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Συγγραφείς:
Sarri, C.A.
Papadopoulos, G.E.
Papa, A.
Tsakris, A.
Pervanidou, D.
Baka, A.
Politis, C.
Billinis, C.
Hadjichristodoulou, C.
Mamuris, Z.
Εκδότης:
Public Library of Science
Λέξεις-κλειδιά:
HLA DP antigen; HLA DPA1 antigen; HLA DQA1 antigen; HLA DRB1 antigen; major histocompatibility antigen class 2; unclassified drug; HLA DP antigen; HLA DQ antigen; HLA DRB1 antigen; HLA-DPA1 antigen; HLA-DQA1 antigen, aged; allele; amino acid sequence; Article; cohort analysis; controlled study; disease course; disease predisposition; disease severity; genetic analysis; genetic variability; human; hydrogen bond; major clinical study; nerve cell lesion; protein binding; protein structure; structure analysis; virus gene; virus infection; West Nile fever; West Nile virus disease; amino acid sequence; binding site; disease resistance; exon; genetic association study; genetic predisposition; genetics; metabolism; molecular model; protein motif; severity of illness index, Amino Acid Motifs; Amino Acid Sequence; Binding Sites; Cohort Studies; Disease Resistance; Exons; Genetic Association Studies; Genetic Predisposition to Disease; HLA-DP alpha-Chains; HLA-DQ alpha-Chains; HLA-DRB1 Chains; Humans; Hydrogen Bonding; Models, Molecular; Severity of Illness Index; West Nile Fever
DOI:
10.1371/journal.pone.0205557
