Andrea L. Cox

Sequence analysis of peptides presented to the immune system by class I and class II MHC molecules

Cytotoxic T lymphocytes (CTL) are an arm of the immune system concerned with recognition of host cells that express new antigens as a result of viral infection. CTL do not recognize new antigens directly, but only as short peptides bound to cell surface class I molecules of the major histocompatability complex (MHC) (Germain, 1986; Monaco, 1992; Morrison et al., 1983). It is thought that a small fraction of newly synthesized self and viral proteins are degraded into small peptides in the cytoplasm, and these are then transported into a subcellular compartment, the endoplasmic reticulum, where they become bound to a groove on the top of class I molecules, and are subsequently transported to the cell surface for presentation to cytotoxic lymphocytes. Class I molecules are glycoproteins consisting of light (12 kDa) and heavy (47 kDa) chains. Each cell presents up to 105 copies of six different class I molecules. Since the cell is also synthesizing several thousand different proteins, each type of class I molecule is expected to present several thousand peptide fragments to the immune system at any particular moment. CTL bind to the class I molecules and check the nature of the peptides being presented. If they are of foreign origin, the CTL become activated, multiply, and lyse the infected cell. If only self peptides are presented, the CTL remain inactive and continue their surveilance of other cells in the neighborhood.