Fig 1.
MHC class II molecules are heterodimers consisting of α (green) and β (orange) chains.
The antigen binding groove is formed by two alpha-helices above a beta-sheet floor. Antigens (red) fit in the cleft and stabilized by electrostatic interactions and/or hydrogen bonds to anchor peptides of the groove (regions with light shades). The structure being illustrated is based on the structure with PDB ID: 2NNA [12].
Fig 2.
The amino acid sequence of exon 2 (partial) of the alleles that were identified in HLA-DPA1, -DQA1 and DRB1 in our WNV cases.
The residues that form pockets P1, P4, P6, P7, P9 and P10 have been noted accordingly. Positions that have the same amino acid with the first sequence in other alleles are shown with dots.
Table 1.
The pocket variants and their frequency found in HLA-DPA1, -DQA1 and -DRB1 in both WNND and WNF case groups.
The pocket in which each variant belongs is shown on the left of the variant. The variants found exclusively in one of the groups are shown in italics (in the WNND/WNF columns).
Fig 3.
The distribution of alleles and pocket variants in WNND (blue) and WNF (light red). Next to each group are listed the alleles that were unique for the group. In the boxes below, the alleles/pocket variants that were associated positively or negatively with neuroinvasion are shown.
Table 2.
List of WNV neuroinvasion-associated amino acid residues in HLA-DQA1 and their properties [25].
P values in bold indicate significance.
Fig 4.
Graphical representation of DQA1/DQB1 molecules.
α chain is shown in red and β chain in green. In the center of the groove, the peptide (chain C from PDB ID: 2NNA) is shown in cyan sticks. The residues of the heterodimer that are in the neighbor of the peptide are shown in CPK colored sticks (DQA1*01:02 in yellow and DQA1*03:01 in magenta). Amino acids from chain β that form H-bonds are shown in salmon. Hydrogen bonds are shown in yellow dotted lines. A. Heterodimer DQA1*01:02-DQB1*03:01. B. Heterodimer DQA1*03:01-DQB1*03:01. All neighbor residues to the peptide are shown (in radius 4 Å). Only the amino acids that form hydrogen bonds are labeled. C. Selected residues that have different orientation and/or show different interaction with the peptide between the two structures (residues 52, 55, 63, 69, 70 and 73). Variable residues of the alleles that were found in close proximity to the peptide are also shown (positions 9, 53, 54 and 59).
Table 3.
All the hydrogen bonds and the salt bridges between DQA/DQB chains and the peptide in both structures.
Columns ‘Molecule 1’/‘Residue’ 1 list the α or β chain of each DQ complex (column ‘Molecule 1’) and the residues that interact with the peptide (column Residue 1). Column ‘Molecule 2’ refers always to the peptide. In column ‘Residue 2’ the peptide’s residues that form H-bonds and salt bridges with any DQ-complex amino acid are listed. The atoms involved are shown.
Table 4.
List of WNV neuroinvasion-associated amino acid residues in HLA-DRB1 and their properties [25].
Fig 5.
Graphical representation of DRA1/DRB1 molecules.
α chain is shown in red and β chain in green. In the center of the groove, the peptide (chain D from PDB ID: 2WBJ) is shown in cyan sticks. The residues of the heterodimer that are in the neighbor of the peptide and belong in P7, P9 and P10 are shown in CPK colored sticks (DRB1*11:04 in yellow and DRB1*14:04 in magenta). Amino acids from chain α that form H-bonds are shown in salmon. Hydrogen bonds are shown in yellow dotted lines. A. Heterodimer DRA1*01– DRB1*11:04. B. Heterodimer DRA1*01– DRB1*14:04. All neighbor residues to the peptide are shown (in radius 4 Å). Only the amino acids that form hydrogen bonds are labeled. C. Selected residues that have different orientation and/or show different interaction with the peptide between the two structures (residues 28, 56, 60, 61 and 82). Variable residues of the alleles that were found in close proximity to the peptide are also shown (positions 57, 67 and 71).
Table 5.
The hydrogen bonds and the salt bridges between DRA/DRB chains and the peptide in both structures.
Columns ‘Molecule 1’/‘Residue’ 1 list the α or β chain of each DR complex (column ‘Molecule 1’) and the residues that interact with the peptide (column Residue 1). Column ‘Molecule 2’ refers always to the peptide. In column ‘Residue 2’ the peptide’s residues that form H-bonds and salt bridges with any DR-complex amino acid are listed. The atoms involved are shown.