Figure 7.

Model for the H. pylori action against the antigen presentation by HLA-II. (A) A common bacterium is engulfed by macrophages (1). Upon killing and digestion in the phagolysosomes (2), bacterial antigens are displayed by HLA-II molecules on the plasma membrane (3). Specific Th1 cells recognize the peptide–HLA-II complexes by TCR and release IFN-γ (4), which activates the transcription of CIITA (5). The increased number of HLA-II-epitopes that can be exposed on the cell surface maximizes the number of T cells activated and amplify the intensity of the ensuing immune response. (B) Macrophages internalize H. pylori antigens released by bacteria (1). Antigens are processed in phagolysosomes (2) and presented in HLA-II to Th1 lymphocytes (3). The latter release IFN-γ (4), but the cytokine action is hindered because of the surrounding/engulfed bacteria (5) that up-regulate the expression of CIITA-targeting miRNAs in macrophages (6). The number of HLA-II molecules does not increase (7) and the activation of Th1 cells with different epitope-specificity is compromised. (C) H. pylori infect macrophages and are phagocytosed (1); bacteria accumulate in megasomes and partial digestion occurs (2); bacterial epitopes are presented in HLA-II to Th1 lymphocytes (3). Concomitantly, the up-regulation of CIITA-targeting miRNAs is elicited (4) and this nullifies the effect of IFN-γ (5), in terms of HLA-II synthesis (6).