Model of antigen processing and presentation in DCs and platelets. (A) Classic pathways of MHC-I pathogen antigen processing in DCs. Exogenous antigens are internalized by DCs and subsequently processed (1) by the vacuolar pathway, by which the antigen is processed in vacuoles and then loaded on MHC-I; (2) by the phagosome-to-cytosol pathway, by which the antigen is taken up by vacuoles and then released into the cytoplasm. (3) Cytosolic antigens are processed by proteasomes and the resulting peptides loaded on MHC-I. Peptide-MHC-I complexes bind to specific T-cell receptors. T-cell proliferation and function are induced, improving survival of mice after infection. (B) Platelet MHC-I reduces CD8⁺ T-cell response in bacterial sepsis. Platelets internalize exogenous antigens. MHC-I is upregulated in platelets during sepsis. Antigen processing in platelets is independent of the platelet proteasome, at least for the model antigen OVA. Processed antigens are expressed by platelets through MHC-I. Interaction of platelet MHC-I with CD8⁺ T-lymphocytes reduces the count of CD8⁺ T-lymphocytes and cytokine release. In a polymicrobial mouse model, this interaction reduced survival.