Linking two immuno-suppressive molecules: indoleamine 2,3 dioxygenase can modify HLA-G cell-surface expression.
Nonclassical human leukocyte antigen (HLA) class I molecule HLA-G and indoleamine 2,3 dioxygenase (INDO) in humans and mice, respectively, have been shown to play crucial immunosuppressive roles in fetal-maternal tolerance. HLA-G inhibits natural killer and T cell function by high-affinity interaction with inhibitory receptors, and INDO acts by depleting the surrounding microenvironment of the essential amino acid tryptophan, thus inhibiting T cell proliferation. We investigated whether HLA-G expression and INDO function were linked. Working with antigen-presenting cell (APC) lines and monocytes, we found that functional inhibition of INDO by 1-methyl-tryptophan induced cell surface expression of HLA-G1 by HLA-G1-negative APCs that were originally cell-surface negative, and that in reverse, the functional boost of INDO by high concentrations of tryptophan induced a complete loss of HLA-G1 cell surface expression by APCs that were originally cell-surface HLA-G1-positive. This mechanism was shown to be posttranslational because HLA-G protein cell contents remained unaffected by the treatments used. Furthermore, HLA-G cell surface expression regulation by INDO seems to relate to INDO function, but not to tryptophan catabolism itself. Potential implications in fetal-maternal tolerance are discussed.
González-Hernandez
Alvaro
A
Clínica Universitaria de Navarra, 31080 Pamplona, Navarra, Spain.
LeMaoult
Joël
J
Lopez
Ana
A
Alegre
Estibaliz
E
Caumartin
Julien
J
Le Rond
Solène
S
Daouya
Marina
M
Moreau
Philippe
P
Carosella
Edgardo D
ED
D002460:Cell Line; D006680:HLA Antigens / Q000096:biosynthesis*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D009000:Monocytes / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D014366:Tryptophan Oxygenase / Q000378:metabolism*; D015854:Up-Regulation
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D014364:Tryptophan; D014366:Tryptophan Oxygenase