Computational Analysis on the Binding of Epitope Peptide to Human Leukocyte Antigen Class I Molecule A*2402 Subtype

Abstract

Major histocompatibility complex (MHC) is a transmembrane glycoprotein that plays an important role in immunological system. Human MHC molecule is usually called as human leukocyte antigen (HLA) and HLA molecules are grouped into class I and II. MHC class I molecule is a heterodimer of heavy chain called a chain, whose mass-weight is 45 kDa, and light chain called b2 micro globulin (b2m) with a mass-weight of 12 kDa. A complex of an HLA and a peptide derived from antigen is displayed on the surface of nucleated cell or platelet. HLA heavy chain has a quite large diversity and thousands of genes have been detected so far, and the number of known genes for HLA heavy chain is still increasing. Each individual has two or three kinds of HLA out of several thousands of HLA genes.Viral protein or cancer-related antigens are detected as foreign molecules in a cell and dissociated by proteasome into peptide fragments consisting of 6-15 amino residues.1) This peptide fragment is bound to HLA class I molecule and the complex is carried to the cell surface in antigen display cells. Cytotoxic T lymphocytes (CTL) expressing T cell receptor recognize the complex, which results in inducing the immunological response to attack the virus-infected or oncogenic cells to exclude virus or tumor. 2)Immunological response has attracted much recent attention because of its potential for immunotherapy. At present, several peptides are assumed to be effective for medical treatment of cancer, leukemia, hepatitis C, and applied to patients in a clinical trial as vaccine through the controlled vaccination.3-5) This peptide-vaccine therapy is expected to lead the regression of disease-related cells without damaging normal tissues. Since the combination of HLA genes has a large diversity, the selection of peptide adequate for each individual is one of the important issues to enhance the performance of immunotherapy.The discovery of a peptide inducing strong immunological response is a key factor in immunotherapy. Since the peptide firmly bound to HLA molecule will be effective as medical material, the search of potent peptide, usually called as epitope, is critically important. In this study, we focus on Wilms' tumor (WT1) protein.6) WT1 protein is encoded in b2 Wilms' tumor gene and overexpressed in leukemic and solid tumor cell. A 9-mer amino acid peptide encoded in WT1 protein was already known to work as an antigenic peptide for HLA-A*2402 molecule. Oka and his co-workers reported the experimental findings that the replacement of the second amino acid residue, which is considered to be deeply responsible for the peptide binding to HLA-A*2402, induced strong immunological response of WT1 specific CTLs compared to the natural peptide. A peptide containing a single amino residue mutation is currently applies for the clinical trial for a vaccination against solid tumor or leukemia. 7)Computer simulation enables us to visualize the interaction of proteins or the interaction of a chemical compound and its target protein. Molecular dynamics (MD) ...

Binding and Aggregation Mechanism of Amyloid β-Peptides onto the GM1 Ganglioside-Containing Lipid Membrane

“…This energy is comparable with the value calculated in the above study. It is interesting to note that these calculated energies are of a degree of affinity similar to the stable peptide–protein interaction as seen in the epitope recognition by human leukocyte antigen …”

Association between HLA and Stevens–Johnson Syndrome Induced by Carbamazepine in Southern Han Chinese: Genetic Markers besides B*1502?

“…The frequency of HLA-A*2402 in the CBZ-induced SJS group was significantly higher than that in the tolerant control group or the southern Han Chinese population. An association between HLA-A*2402 and any cADRs has not been reported before, although a HLA-A*2402 activated immune response by interacting with antigenic peptide of some tumour proteins has been revealed previously [22,23]. Further studies are required to verify the association between HLA-A*2402 and CBZ-induced SJS.…”

Binding characteristics of staphylococcal protein A and streptococcal protein G for fragment crystallizable portion of human immunoglobulin G

“…The nonpolar solvation free energy difference is measured by estimating the approximate linear fitting relationship of the solvent-accessible surface area (SASA) difference. Subsequently, the change in the conformational entropy ( ) is set equal to 0.0 in this study because the influence of this entropic term on a similar protein–protein binding complex is negligible [33] , [63] . Finally, the binding free energy, which has a less structural RMSD fluctuation, is summed and averaged over the selected trajectory periods.…”

“…These shortcomings of previous methods can be resolved by leveraging computational studies enabling the detailed investigation of mechanisms behind the reversible binding of receptor–ligand complexes in terms of ionic and hydrophobic interactions, hydrogen bonds, and van der Waals (vdW) forces [33] , [79] . However, there have been no in-depth studies on IgG-spA/spG complexes, even though they are the most prevalent combination in affinity chromatography.…”

“…However, there have been no in-depth studies on IgG-spA/spG complexes, even though they are the most prevalent combination in affinity chromatography. This is because most of the few direct and quantitative measurement studies on protein binding have been primarily focused on monomeric ligand complexes (e.g., linear short peptide with a small amount of residue rather than multimeric complexes) [33] , [34] , [35] , [36] , [37] . Moreover, the studies on larger ligands have been hampered by the inconvenience of modeling many rotatable bonds in flexible peptides and obtaining accurate high-resolution models of binding interfaces [38] .…”