Lipoprotein access to MHC class I presentation during infection of murine macrophages with live mycobacteria.
Following uptake by macrophages, live mycobacteria initially reside within an immature phagosome that resists acidification and retains access to recycling endosomes. Glycolipids are exported from the mycobacterial phagosome and become available for immune recognition by CD1-restricted T cells. The aim of this study was to explore the possibility that lipoproteins might similarly escape from the phagosome and act as immune targets in cells infected with live mycobacteria. We have focused on a 19-kDa lipoprotein from Mycobacterium tuberculosis that was previously shown to be recognized by CD8(+) T cells. The 19-kDa Ag was found to traffic separately from live mycobacteria within infected macrophages by a pathway that was dependent on acylation of the protein. When expressed as a recombinant protein in rapid-growing mycobacteria, the 19-kDa Ag was able to deliver peptides for recognition by MHC class I-restricted T cells by a TAP-independent mechanism. Entry into the class I pathway was rapid, dependent on acylation, and could be blocked by killing the mycobacteria by heating before infection. Although the pattern of 19-kDa trafficking was similar with different mycobacterial species, preliminary experiments suggest that class I presentation is more efficient during infection with rapid-growing mycobacteria than with the slow-growing bacillus Calmette-Guérin vaccine strain.
Neyrolles
O
O
Department of Infectious Diseases and Microbiology, Imperial College School of Medicine, St. Mary's Campus, London, United Kingdom. olivier.neyrolles@sls.ap-hop-paris.fr
Gould
K
K
Gares
M P
MP
Brett
S
S
Janssen
R
R
O'Gaora
P
P
Herrmann
J L
JL
Prévost
M C
MC
Perret
E
E
Thole
J E
JE
Young
D
D
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D008074:Lipoproteins / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009161:Mycobacterium / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
C087864:19 kDa antigen, Mycobacterium; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015395:Histocompatibility Antigens Class I; D008074:Lipoproteins; D011994:Recombinant Proteins