Compartmentalization of bacterial antigens: differential effects on priming of CD8 T cells and protective immunity.
Bacterial pathogens synthesize numerous proteins that are either secreted or localized within bacterial cells. To address the impact of antigen compartmentalization on T cell immunity, we constructed recombinant Listeria monocytogenes that express a model CD8T cell epitope as a secreted or nonsecreted fusion protein. Both forms of the antigen, either secreted into the host cell cytoplasm or retained within bacterial cells, efficiently prime CD8 T cell responses. However, epitope-specific CD8 T cells confer protection only against bacteria secreting the antigen but not against the bacteria expressing the nonsecreted form of the same antigen. This dichotomy as a result of antigen compartmentalization suggests that bacterial antigens are presented by multiple MHC class I pathways to prime CD8 T cells, but only the endogenous pathway provides target antigens for CD8 T cell-mediated protective immunity.
Shen
H
H
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Miller
J F
JF
Fan
X
X
Kolwyck
D
D
Ahmed
R
R
Harty
J T
JT
D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002451:Cell Compartmentation / Q000276:immunology*; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology; D007110:Immunity, Active / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D000939:Epitopes; D011993:Recombinant Fusion Proteins