Linking Two Immuno-Suppressive Molecules: Indoleamine 2,3 Dioxygenase Can Modify HLA-G Cell-Surface Expression

• Published in: Biology of reproduction 2005-09, Vol.73 (3), p.571-578
• Main Authors: GONZALEZ-HERNANDEZ, Alvaro, LEMAOULT, Joël, LOPEZ, Ana, ALEGRE, Estibaliz, CAUMARTIN, Julien, LE ROND, Solène, DAOUYA, Marina, MOREAU, Philippe, CAROSELLA, Edgardo D
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Line; Embryology: invertebrates and vertebrates. Teratology; Fetal membranes; Fundamental and applied biological sciences. Psychology; General aspects. Development. Fetal membranes; Histocompatibility Antigens Class I - biosynthesis; HLA Antigens - biosynthesis; HLA-G Antigens; Humans; Monocytes - immunology; Protein Processing, Post-Translational - drug effects; Protein Processing, Post-Translational - physiology; Tryptophan - analogs & derivatives; Tryptophan - pharmacology; Tryptophan - physiology; Tryptophan Oxygenase - metabolism; Up-Regulation; Vertebrates: reproduction
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.105.040089

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. Abstract IDO activity alters HLA-G cell-surface expression