ABSTRACT

Major histocompatibility complex (MHC) class I molecules are expressed on all mammalian cells. They present peptide fragments of intracellular pathogens at the cell surface for consideration by the immune system. The so-called cytotoxic T cells (CTLs) can recognize these and then decide to kill the infected cell. The process of antigen presentation by MHC class I molecules is understood in detail. It involves a number of steps dedicated to ensuring that antigenic fragments are only presented to the immune system by infected cells and not by innocent bystanders. This can be achieved by retaining antigenic fragments in the infected cell, which prevents the elimination of non infected neighboring cells by immune cells, or-in immunology languageprevents innocent bystander kill. However, activation of T cells also requires presentation of peptide fragments by dendritic cells (DCs) that act as master regulators in the immune system. The fact that these DCs present fragments that are derived from other cells means that they are able to break the dogma of classical MHC class I antigen presentation where antigenic peptides are presented only by the infected cells. Recently, peptides have been shown to diffuse through gap junctions. This allows peptides to be transferred from an infected cell to its neighbor for presentation by the noninfected cell and then allows innocent bystander kill. Connexins are expressed in the immune system under various conditions, but were not really considered to be important by the

5.1 Standard Model of Antigen Presentation by MHC Class I Molecules ...........90 5.2 An Exception: Antigen Cross-Presentation via Gap Junctions ......................90 5.3 Innocent Cells Do Not Die in Vain .................................................................93 5.4 Gap Junctions in T Cell Activation .................................................................94 5.5 Summary ........................................................................................................96 References ................................................................................................................96