GCB2011 Junior Paper Docking Peptides into MHC Class II Complexes

The interaction between T-cell receptor (TCR) complexes exposed on CD4⁺ T lymphocytes and exogenous antigenic peptides (p) displayed by dimeric, major histocompatibility complex class II protein complexes (MHCII) constitutes a significant step in the activation of humoral immunity. As TCRs can only bind to MHCII-presented antigenic peptides, the binding of peptides to MHCII is a crucial bottleneck within adaptive immune responses. Therefore, the knowledge about which peptides bind to a particular MHCII is of interest in many medical applications. The high sequence variation of MHCII and the great reservoir of potential MHCII-binding peptides significantly raise costs for experimental approaches aiming to determine MHCII-peptide binding data. Therefore, a plethora of sequence-based bioinformatics approaches has been developed. Here, we present a new structure-based approach to computationally model the p-MHCII interaction on the basis of the previously published IRECS algorithm in combination with the ROTA potentials^2,3. The method allows modeling high quality complex structures and shows a good correlation between the RMSD of the modeled structures and the corresponding peptide binding score.