Evasion of peptide, but not lipid antigen presentation, through pathogen-induced dendritic cell maturation.
Dendritic cells (DC) present lipid and peptide antigens to T cells on CD1 and MHC Class II (MHCII), respectively. The relative contribution of these systems during the initiation of adaptive immunity after microbial infection is not characterized. MHCII molecules normally acquire antigen and rapidly traffic from phagolysosomes to the plasma membrane as part of DC maturation, whereas CD1 molecules instead continually recycle between these sites before, during, and after DC maturation. We find that in Mycobacterium tuberculosis (Mtb)-infected DCs, CD1 presents antigens quickly. Surprisingly, rapid DC maturation results in early failure and delay in MHCII presentation. Whereas both CD1b and MHCII localize to bacterial phagosomes early after phagocytosis, MHCII traffics from the phagosome to the plasma membrane with a rapid kinetic that can precede antigen availability and loading. Thus, rather than facilitating antigen presentation, a lack of coordination in timing may allow organisms to use DC maturation as a mechanism of immune evasion. In contrast, CD1 antigen presentation occurs in the face of Mtb infection and rapid DC maturation because a pool of CD1 molecules remains available on the phagolysosome membrane that is able to acquire lipid antigens and deliver them to the plasma membrane.
Hava
David L
DL
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA.
van der Wel
Nicole
N
Cohen
Nadia
N
Dascher
Christopher C
CC
Houben
Diane
D
León
Luis
L
Agarwal
Sandeep
S
Sugita
Masahiko
M
van Zon
Maaike
M
Kent
Sally C
SC
Shams
Homayoun
H
Peters
Peter J
PJ
Brenner
Michael B
MB
D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D001693:Biological Transport, Active / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
D018949:Antigens, CD1; C419394:CD1b antigen; D000949:Histocompatibility Antigens Class II; D008055:Lipids; D010455:Peptides