AminoAcid3D: An Algorithm for Designing HLA Single Antigen Panels and Predicting the Essential Regions of Epitopes...

The highly polymorphic yet homologous nature of HLA antigens (Ags) constitutes a milieu of public and private B-cell epitopes of varying degrees far exceeding the coverage of the existing cross-reactive groups (CREGs). To support the on-going efforts in updating serological categorisation and designing the next generation single antigen bead (SAB) panel of higher resolution and broader population coverage, an algorithm named AminoAcid3D (AA3D) has been developed as a research tool for designing SAB panels and predicting which amino acid residues (termed 'eps') could be involved in Ag-antibody (Ab) interactions according to SAB reactivity profiles. AA3D discerns patterns directly based on Ag sequence and structure, allows size flexibility of contact area and accommodates the uncertainties involving molecular modelling, without pre-filtering and/or pre-assigning eps based on polymorphism or predicted attributes such as solvent exposure, protruding index, physicochemical properties, and so forth. Therefore, AA3D enables a more comprehensive approach in capturing various scenarios manifested in the SAB assay. After the eps are indicated using AA3D based on experimentally determined reactivity profiles, further filters can then be applied to rank their probability as the specificity determinants and epitope participants. AA3D provides a powerful research tool for systematic evaluation of spatial parameters that predicts the essential residue(s)/region for specificity of an epitope from a single ep to a cluster of increasing size. Data collected and knowledge gained with AA3D contribute to defining HLA serology. The concepts, hypotheses, algorithms, designs, applications, examples and future directions are described and discussed.