[Molecular basis for detection of infectious agents].

Elimination of foreign pathogens requires detection of the presence of such microorganisms somewhere in the body. This task relies on specialized cells, among which specific lymphocytes permanently circulate throughout the body searching for signals indicative of the presence of invasive microorganisms. In contrast to B lymphocytes, T lymphocytes are unable to recognize bacteria or viruses in their native form. The structure of their antigen receptor only allows them to bind to small peptidic fragments that have to be stably presented by specific molecules at the surface of specific cells. These professional "antigen presenting cells" capture antigens and alert the immune system by expressing at their surface molecular complexes formed by their own major histocompatibility molecules (MHC) and fragments of the infectious agent. Extracellular microorganisms are captured by phagocytosis and digested into small peptides in the endosomal compartment of antigen presenting cells. The peptides able to bind to MHC class II molecules are transported to the cell surface. These antigen-MHC complexes are recognized by antigen specific CD4+ T lymphocytes, thus leading to the enhancement of antibody formation and of inflammatory responses which eliminate extracellular bacterial. In contrast, viruses or bacteria able to survive within the cytoplasm of the antigen presenting cells are digested by a specific multicatalytic enzymatic complex (the proteasome). The antigenic peptides released into the cytosol will be transported into the endoplasmic reticulum by an active peptide pump. The peptides able to bind to the groove of MHC class I molecules are transported to the cell surface. Their recognition by specific cytotoxic CD8+ lymphocytes leads to the destruction of the cells identified as infected. Thus, the mechanisms of antigen processing and presentation are able to generate a wide variety of antigenic fragments. Depending on the initial extra- or intracellular localization of the microorganism, some antigenic peptides will appear on the surface of antigen presenting cells on either MHC class I or class II molecules which are specifically recognized by either CD4+ or CD8+ lymphocytes. Only the antigenic peptides that are generated by this process and able to bind to MHC molecules of antigen presenting cells will be recognized by circulating lymphocytes and thus induce antigen specific immune response. Their identification therefore forms the basis of the defense mechanisms against infectious diseases and of novel immunization strategies.