The processing and presentation of Listeria monocytogenes antigens by macrophages.

Macrophages play a requisite role in the induction and expression of T lymphocyte responses to Listeria monocytogenes. For effective T cell-macrophage interaction to occur, macrophages must perform at least two fundamental functions. They must take up and handle the antigen, and they must express appropriate membrane glycoproteins encoded for by the I-region of murine major histocompatibility gene complex (Ia molecules). Data collected in a murine model suggests that the following sequential events are involved in the Listeria-macrophage-T cell interaction. Listeria interaction with macrophage cell surface via trypsin sensitive structures. Interiorization within phagosomes. Phagosome-lysosome fusion. Partial degradation of Listeria. Transfer of protein antigen fragments to macrophage cell surface. Recognition of macrophage surface antigen and I-region associated (Ia) molecules by the T cell receptor. The essential feature of this model is that: antigen handling occurs intracellularly and independently of macrophage cell surface Ia molecules. With regard to the survival advantage of this mechanism, one may speculate that the degradation of pathogens by macrophages may serve to increase the number of different structural moieties which can act as antigens. Thus, bacterial components normally sequestered in the interior of organisms could conceivably serve as antigens, and the multiplicity of such antigenic determinants would make it less likely that a nonresponder status with respect to I-region gene function would be generated. This mechanism may be especially relevant to host defense against intracellular pathogens such as Listeria monocytogenes.