Présentation antigénique par les cellules dendritiques.

Abstract

Pour entrainer une reponse immune, l' antigene stimulant doit etre presente au lymphocyte T CD8+ (reponse cytolytique) ou CD4+ (reponse auxiliaire) par une molecule du CMH, respectivement de classe I ou II. Parmi les cellules presentatrices de l' antigene, les cellules dendritiques sont les plus performantes: elles ont la capacite non seulement d' activer des lymphocytes T naifs, mais aussi d' induire une reponse humorale et cytolytique par leur presentation d' antigenes par les molecules de classe I ou II du CMH. Les etapes du catabolisme de l' antigene sont strictement correlees aux stades de la maturation des cellules dendritiques: seules les cellules dendritiques immatures, concentrees dans les tissus pheripheriques, peuvent phagocyter et provoquer l' endocytose des antigenes solubles et particulaires, mais elles ne peuvent pas, a ce stade, les presenter aux lymphocytes T car les molecules du CMH sont retenues dans les lysosomes. En revanche, le processus de maturation de ces cellules, controle par des signaux inflammatoires et par le couple CD40-L/CD40, s' accompagne de changements morphologiques, de la relocalisation des molecules de classe II du CMH a la membrane, de l' expression de molecules de co-stimulation lymphocytaire, et surtout de la migration des cellules dendritiques des tissus peripheriques vers les ganglions et la rate. Dans ces organes, la cellule dendritique mure est apte a presenter aux lymphocytes CD4+ l' antigene proteolyse en peptides et complexe aux molecules du CMH-II.

The stimulation of T lymphocytes requires the presentation of proteolytic antigen-derived peptides by major histocompatibility complex (MHC) molecules. All cells in the organism express MHC class I molecules, which present peptides derived from endogenous antigens to cytotoxic T cells. In contrast, only a few cell types, mainly from hematopoietic origin, express MHC class II molecules and are capable of stimulating helper CD4+ T lymphocytes. One of these cell types, dendritic cells (DC), have the unique capacity to stimulate naive T lymphocytes and initiating primary and secondary immune responses. This unique role of DCs relies on three specific attributes of this particular antigen presenting cells. First, their capacity to undergo a series of phenotypical and functional changes (maturation) in response to inflammatory signals. These modifications cause the migration of DCs from peripherical tissues and mucosa (where DCs reside in their immature state) towards secondary lymphoid org ans, where DCs may stimulate resting T lymphocytes. Second, a tightly regulated MHC class II antigen presentation capacity. Only immature DCs ingest and process antigens, whereas only the mature ones present peptides to CD4+ T lymphocytes. Finally, a unique ability to present peptides from exogenous antigens, internalized from the extracellular milieu, on MHC class I molecules. Together, these specific attributes confer to DCs a central role in the initiation of both humoral and cellular immune responses.