Major Histocompatibility Complex – Immunopeptidome current data

Major Histocompatibility Complex (MHC) is a highly polymorphic and polygenic system that is responsible for the encoding of HLA antigens. The genes of MHC are organized in three clusters: class I and class II regions, which encode HLA antigens, and class III region. They are inherited according to Mendel's laws as a whole. HLA antigens are consisted of two heavy and two light chains. Also, they have a binding groove, which binds the peptide of foreign antigens. Class I HLA molecules are located to the membrane of all nucleated cells. In contrast, class II HLA molecules are located to some antigen presenting cells (APCs). The binding groove of HLA class I molecules binds endogenous antigens and presents them to CD8 cells, while HLA class II molecules present exogenous antigens to CD4 cells. This phenomenon is called MHC restriction. The major biological role of this system is the control of the immune response. MHC function is applied to many medical fields, such as transplantations, immune resistance to some diseases and mate choice.

Nowadays, a new area, which is called MHC-immunopeptidomic, is being researched. MHC-immunopeptidomic studies the countless peptides presented to the cell surface by MHC molecules, which consist the immunopeptidome. The immunopeptides are derived to two clusters: class I peptides and class II peptides. These peptides are products of protein degradation. Class I peptides are the most interesting, since they derive from endogenous proteins. Endogenous proteins of great importance are the rapidly degraded polypeptides (RDPs). RDPs are derived to Short Lived Proteins (SLiPs) and Defective Ribosomal Products (DRiPs). Although the structure of DRiPs is not entirely defined, it is supported that DRiPs are responsible for the rapid recognition of the viral antigens and they are connected to tumor immunosurveillance. MHC-immunopeptidome could offer new aspects to cancer immunotherapy, vaccines and autoimmunity. A newborn mass spectrometry method, which is called SWATH-MS, consists a new tool for studying MHC-immunopeptidome.