MHC molecules report cellular health by presenting endogenous and exogenous peptides to T cells. In order to characterize T cell receptor recognition, we need to obtain detailed surface features of the pMHC complexes oriented to T cell receptors. Therefore, we need high-resolution structural models of the pMHC complexes.

Based on the structural analysis of pMHC, Creative BioMart offers efficient and reliable pMHC modeling tools to determine the 3D structure of pMHC complexes through this interesting and creative solution, thus revealing the molecular basis of important immune responses.

pMHC Structural Analysis

MHC binds to intracellular peptides or exogenous peptides and combines to form pMHC complexes that are transported to the cell surface, where T cells examine the pMHC to determine whether a given cell is diseased or healthy. Generally diseased cells display peptides different from those presented by healthy cells, and if T cells are able to recognize such different peptides, an immune response is triggered. The ultimate immune response is triggered by the appropriate interaction of the T cell receptor (TCR) and pMHC, so a full understanding of the process requires more in-depth analysis than just a simple comparison of peptide sequences, but also from a structural perspective.

It has been shown that similar peptide sequences in contact with the TCR may produce different pMHC surfaces, while different peptide sequences can present almost identical pMHC surfaces. This specific structural role can be obtained by X-ray crystallography and NMR spectroscopy, but it has the limitations of being expensive and time-consuming. pMHC modeling is based on a reliable validation process and careful structural studies that can take into account a wide range of pMHC specificities. It can help us to understand exactly the sequence-structure correspondence and is essential for the use of immune molecular mechanisms for the treatment of certain diseases.

Our pMHC Modeling Services

We provide pMHC modeling methods to predict pMHC structural models using structural templates from the Protein Data Bank, mainly including MHC and epitope structures.

Fig.1 Service flow of pMHC modeling

• Use automated modeling tools to perform the steps according to the process.
• Linear amino acid sequences are used as modeling epitopes, and tools are used to assign shape to the modeled epitopes.
• Prepare MHC molecules and model epitopes on the modeled epitopes and dock the best pMHC complexes generated by the first molecule.
• The best epitope conformational composition is selected from the docking output and confirmed by analysis of quantitative data as well as verification by T-cell assay.

Applications

• Immune recognition of viral infections. Presumptive immunogenic pMHCs are screened by our structural computational analysis to determine whether they can effectively clear the virus.
• Identification of tumor-specific antigens. Computerized structural methods and other data analysis are used to select the best immunogenic peptides to build personalized vaccine designs for application to different tumor types.

The study of pMHC molecules at the structural level is essential for understanding the molecular mechanisms of the immune response. Creative BioMart provides researchers with a reliable web-based pMHC modeling service that builds on existing protein database structures to construct pMHC complexes in an automated and efficient manner, providing structural modeling results to help understand important events in the immune response.

If you would like more information about our services, a project quote or professional consultation, please contact us.

Reference

• Menegatti Rigo M, et al. "DockTope: a Web-based tool for automated pMHC-I modelling." Sci Rep (2015),5,18413.