Isolation and Characterization of Naturally Processed MHC-Bound Peptides From the Surface of Antigen-Presenting Cells.

The human major histocompatibility complex (MHC) is located on the short arm of chromosome 6 and encompasses approx 4 Mb, or 0.1%, of the genome. This region is, by far, the most polymorphic of the human genome. More than 220 genes have been identified in this region and at least 10% of these genes have a direct function in immune responses. The human MHC can be divided into three regions that encode the class I, class II, and class III human leukocyte antigen (HLA) gene products. These HLA molecules demonstrate tremendous polymorphism, which reflects the natural evolution of these genes in response to various microbial pathogens in different ethnic populations. HLA class I molecules are expressed on all nucleated cells and associate with short peptides (8-11 amino acids in length) derived from both self and foreign antigens. These peptide ligands are primarily generated in or transported into the cytoplasm and subsequently translocated into the endoplasmic reticulum (ER) where they assemble with nascent MHC class I molecules. These mature, peptide-loaded, complexes are then transported to the cell surface where they are scrutinized by CD8+ cytotoxic T lymphocytes (CTL). Should the peptide ligand be derived from a pathogen and be recognized as foreign in an immunocompetent host, the cell is killed via the cytotoxic armory of the CTL. The expression of HLA class II molecules is confined to a small subset of highly specialized cells called antigen-presenting cells (APCs). [ABSTRACT FROM AUTHOR]