A modular concept of HLA for comprehensive peptide binding prediction

Abstract

A variety of algorithms have been successful in predicting human leukocyte antigen (HLA)-peptide binding for HLA variants for which plentiful experimental binding data exist. Although predicting binding for only the most common HLA variants may provide sufficient population coverage for vaccine design, successful prediction for as many HLA variants as possible is necessary to understand the immune response in transplantation and immunotherapy. However, the high cost of obtaining peptide binding data limits the acquisition of binding data. Therefore, a prediction algorithm, which applies the binding information from well-studied HLA variants to HLA variants, for which no peptide data exist, is necessary. To this end, a modular concept of class I HLA-peptide binding prediction was developed. Accurate predictions were made for several alleles without using experimental peptide binding data specific to those alleles. We include a comparison of module-based prediction and supertype-based prediction. The modular concept increased the number of predictable alleles from 15 to 75 of HLA-A and 12 to 36 of HLA-B proteins. Under the modular concept, binding data of certain HLA alleles can make prediction possible for numerous additional alleles. We report here a ranking of HLA alleles, which have been identified to be the most informative. Modular peptide binding prediction is freely available to researchers on the web at http://www.peptidecheck.org .

Major histocompatibility complex class I binding predictions as a tool in epitope discovery

“…no or few examples of binding peptides are known). [73][74][75][76][77][78] This type of predictor is, in the following text, referred to as being pan-specific. In the only benchmark performed so far, NetMHCpan was validated as the best of the methods compared, 79 and a recent update of this method is able to accurately predict peptide binding even for MHCs from several non-human mammals.…”

The nature of peptides presented by an HLA class I low expression allele

“…A B residues contacting positions P2, P3 and PΩ of the bound peptides (Table 2) to find the reason for the lack of an auxiliary anchor at P2 of the A*30 derived peptides as described by Lamberth et al 15 When compared with the modules for P2 (Module Explorer, www.histocheck.org), 23,24 no auxiliary anchor at P2 was found for A*1101 or A*3001/14L. According to the Chelvanayagam pocket definition, a module is defined as all amino acids of an HLA molecule forming the respective pocket which binds a certain position of the peptide.…”

Genetics of graft-versus-host disease: The major histocompatibility complex

“…In turn, allele and antigen mismatches reflect the ethnic background of the transplant patient and donor. Parallel efforts are in progress to apply statistical and structural modelling to identify (non)permissive HLA mismatches 78-81 .…”