Toward the Prediction of Class I and II Mouse Major Histocompatibility Complex-Peptide-Binding Affinity
- Channa K. HattotuwagamaAffiliated withThe Jenner Institute, University of Oxford
- , Irini A. DoytchinovaAffiliated withThe Jenner Institute, University of Oxford
- , Darren R. FlowerAffiliated withThe Jenner Institute, University of Oxford
* Final gross prices may vary according to local VAT.Get Access
Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide–major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods—a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method—which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities ( IC50 ) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide–MHC affinity.
We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A * 0101, HLA-A * 0201, HLA-A * 0202, HLA-A * 0203, HLA-A * 0206, HLA-A * 0301, HLA-A * 1101, HLA-A * 3101, HLA-A * 6801, HLA-A * 6802, HLA-B * 3501, H2-Kk, H2-Kb, H2-Db HLA-DRB1 * 0101, HLA-DRB1 * 0401, HLA-DRB1 * 0701, I-A b , I-A d , I-A k , I-A s , I-E d , and I-E k.
In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made are freely available online at the URL http://www.jenner.ac.uk/MHCPred.
Key WordsMajor histocompatibility complex peptides/epitopes QSAR additive method CoMSIA
- Toward the Prediction of Class I and II Mouse Major Histocompatibility Complex-Peptide-Binding Affinity
- Book Title
- Book Subtitle
- Predicting Immunogenicity In Silico
- Book Part
- Part III
- pp 227-245
- Print ISBN
- Online ISBN
- Series Title
- Methods in Molecular Biology™
- Series Volume
- Series ISSN
- Humana Press
- Copyright Holder
- Humana Press Inc.
- Additional Links
- Major histocompatibility complex
- additive method
- Industry Sectors
- eBook Packages
To view the rest of this content please follow the download PDF link above.