DC targeting by a bacterial OmpA

Abstract

In their recent article, Jeannin et al. 1xOmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway. Jeannin, P et al. Nat. Immunol. 2000; 1: 502–509Crossref | PubMedSee all References1 used a bacterial outer membrane protein from Klebsiella pneumoniae (kpOmpA) to target antigen to the major histocompatibility (MHC) class I compartment of dendritic cells (DCs). They isolated recombinant kpOmpA (previously called P40) and showed it binds to DCs and macrophages, and is internalized by immature DCs and macrophages via receptor-mediated endocytosis. This leads to maturation of DCs and cytokine release. Signalling involves Toll-like receptor 2 (TLR2) with no facilitation by CD14. Jeannin et al. coupled protein antigens to kpOmpA and demonstrated that the coupled antigens are presented to T cells by DCs on MHC class I in a transporter associated with antigen processing (TAP)-dependent manner. Coupling to kpOmpA reduces the concentration of antigen needed to induce a T-cell response, suggesting specific targeting of the protein to the cell and/or the class I presentation pathway by kpOmpA. Similarly, in vivo, after injection, coupled protein antigen or peptide is detected on CD11c? cells and induces a cytotoxic T lymphocyte (CTL) response. Using ovalbumin as a model tumour antigen, after immunization of mice with kpOmpA–ovalbumin there is induction of a protective immune response against tumour formation in vivo. Bacterial kpOmpA could therefore be used to target exogenous antigens to the cross-priming pathway of DCs for presentation by MHC class I to T cells. Outer membrane proteins of Gram-negative bacteria are already known to be highly immunogenic for CD4? T cell and antibody responses. This might be explained by the ability of professional antigen presenting cells to bind and internalize some of these proteins, allowing presentation to T cells. Macrophage receptor-mediated internalization of bacteria via outer membrane protein interactions might also help to increase clearance of bacteria from the host.