Molecular interaction of CD1b with lipoglycan antigens.
The ability of human CD1b molecules to present nonpeptide antigens is suggested by the T cell recognition of microbial lipids and lipoglycans in the presence of CD1b-expressing antigen-presenting cells. We demonstrate the high-affinity interaction of CD1b molecules with the acyl side chains of known T cell antigens, lipoarabinomannan, phosphatidylinositol mannoside, and glucose monomycolate. Furthermore, CD1b-antigen binding was optimal at acidic pH, consistent with the known requirement for endosomal acidification in CD1b-restricted antigen presentation. The mechanism for CD1b-ligand interaction involves the partial unfolding of the alpha helices of CD1b at acidic pH, revealing a hydrophobic binding site that could accommodate lipid. These data provide direct evidence that the CD1b molecule has evolved unique biochemical properties that enable the binding of lipid-containing antigens from intracellular pathogens.
Ernst
W A
WA
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095, USA.
Maher
J
J
Cho
S
S
Niazi
K R
KR
Chatterjee
D
D
Moody
D B
DB
Besra
G S
GS
Watanabe
Y
Y
Jensen
P E
PE
Porcelli
S A
SA
Kronenberg
M
M
Modlin
R L
RL
D000817:Anilino Naphthalenesulfonates; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology; D010716:Phosphatidylinositols / Q000276:immunology; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000276:immunology; D013050:Spectrometry, Fluorescence; D001613:beta 2-Microglobulin / Q000276:immunology*
D000817:Anilino Naphthalenesulfonates; D000942:Antigens, Bacterial; D018949:Antigens, CD1; D006017:Glycolipids; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; C048938:glucose mycolate; C050016:lipoarabinomannan; C034154:phosphatidylinositol mannoside; C027132:1-anilino-8-naphthalenesulfonate