MHC binding peptides prediction – Immunology – Antigens/Epitotes/Pools/Librairies

Major Histocompatibility Complex (MHC),also known as the Human Leukocyte Antigens (HLA),is a group of genes that code for cells surface proteins. MHC molecules help the adaptive immune system to detect foreign substances by displaying endogenous or exogeneous antigens on their surface to enable their recognition by the appropriate T-cells. Even though MHC is highly polygenic and polymorphic,the encoded molecules expressed on the cell's surface can be divided in two subclasses known as MHC class I and MHC class II. MHC class I proteins are expressed on all cells but red blood cells to present endogenous epitopes to Cytotoxic T-Cells (CTL or CD8+ T-cells). They are formed by one polypeptide chain constituted of three external domains (α1,α2,α3) and one constant region,called β2-microglobulin,presented on Figure 1 below. On the other hand,MHC class II molecules are only expressed on Antigen Presenting Cells (APC),such as macrophages,B cells,and especially dendritic cells (DC). MHC class II proteins bind to exogeneous antigens to enable their detection by helper T-Cells (TH-cells or CD4+ T-cells). Class II MHC proteins structurally differs from the 1st class by being composed of two polypeptide chains constituted of two external domains each (α1,α2 and β1 , β2),depicted on Figure 2 below. Unlike the innate immunity,the adaptive immune system is highly specific to each pathogen the body has been exposed to. This immunity strategy is involved in immunization modulation by creating immunological memory. Among the cells involved in adaptive immunity processes,T-cells require MHC proteins to recognize pathogenic antigens. These immune cells display T-Cells Receptors (TCR) on their surface that is non-covalently associated with a complex of proteins known as CD3 and the ξξ homodimer. The TCR complex (Figure 3 hereafter) is identical in all T-cells,but the co-receptors,thanks to which the appropriate T-cells recognize the corresponding MHC molecules,differ depending on the type of T-cells recruited i.e. CD4 or CD8 co-receptors for CTL or TH-cells,respectively. Once the foreign epitope recognized by the corresponding T-cell,pre-programmed cell death via apoptosis will be initiated by CTL and naïve CD4+ T-cells will be activated in TH-cells that differentiate in memory or effector TH-cells to modulate immunization. Nowadays,the specific activation of T-cells via MHC binding peptides is a highly valuable process to develop personalized cancer vaccines. Indeed,cancer cells express modified MHC molecules that are difficult to detect by the immune system. Fortunately,the synthesis of peptides able to bind these MHC proteins would enable the normal recognition and processing of tumor cells by immune cells. To help design these synthetic peptides,various predictors were developed with free or paying access. Here is a non-exhaustive list of MHC peptide binding predictors: 1.IEDB is a complete and powerful platform to identify MHC binding peptides,predict B-cell and T-cell epitopes and much more. 2.NetMHC allows to predict allele-specific binding peptides to MHC class I. 3.Predicts peptide-MHC binding using the stabilized matrix method (SMM) algorithm with a specifically constructed amino acid substitution matrix. 4.The NetMHCpan-4.1 server predicts binding of peptides to any MHC molecule of known sequence using artificial neural networks (ANNs). 5.The NetMHCcons 1.1 server predicts binding of peptides to any known MHC class I molecule. 6.SYFPEITHI database comprises more than 7000 peptide sequences known to bind class I and class II MHC molecules. 7.AntiJen v2.0,is a database containing quantitative binding data for peptides binding to MHC Ligand,TCR-MHC Complexes,T Cell Epitope,TAP,B Cell Epitope molecules and immunological Protein-Protein interactions. In addition,AntiJen has recently included Peptide Library,Copy Numbers and Diffusion Coefficient data. 8.The database provides information about allele specific MHC binding peptides,MHC non-binding,TAP binding,TAP non-binding peptides and T-cell epitopes reported in literature. IC-PEPTIDE is a France-based company highly-specialized in peptides manufacturing and analysis. We offer a wide range of products and services dedicated to immunologists,including: 1.Custom peptide synthesis: short to long peptides,cyclized,biotinylated,fluorescent,conjugated to KLH/BSA,... 2.Synthesis of peptide libraries: peptide synthesis in 96 well-plates,fro 25€ / peptide 3.Customized peptide pool: preparation of specific pools containing crude or purified peptides 4.Catalog of antigens,epitopes,peptide pools (infection,cancer,control) 5.Analytical services: SEC-HPLC MHC,mass spectrometry...

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