Published online before print April 7, 2005

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(Journal of Leukocyte Biology. 2005;78:95-105.)
© 2005 by Society for Leukocyte Biology

HLA-DO transduced in human monocyte-derived dendritic cells modulates MHC class II antigen processing

Angélique Bellemare-Pelletier^*, Jessy Tremblay^*, Sylvie Beaulieu, Mohamed-Rachid Boulassel, Jean-Pierre Routy, Bernard Massie, Réjean Lapointe^¶ and Jacques Thibodeau^*,1

^* Laboratoire d’Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Québec, Canada;
Laboratoire d’Immunologie, Hôpital Saint-Luc, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Québec, Canada;
Division of Hematology and Immunodeficiency Service, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada;
Institut de recherche en biotechnologie, Montréal, Québec, Canada; and
^¶ Laboratoire d’immunologie, Hôpital Notre-Dame, Centre hospitalier de l’Université de Montréal, Québec, Canada

¹ Correspondence: Laboratoire d’Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, CP 6128, Succursale Centre-Ville, Montréal, Québec, Canada, H3C 3J7. E-mail: Jacques.Thibodeau{at}umontreal.ca

Through the regulation of human leukocyte antigen (HLA)-DM (DM) in B cells, HLA-DO (DO) modulates positively or negatively the presentation of specific peptides. Transduction of DO into human blood monocyte-derived dendritic cells (MoDC) has been proposed as a mean of modifying the peptide repertoire of major histocompatibility complex class II molecules. However, maturation of DC induced by inflammatory stimuli or possibly the adenoviral vector itself triggers acidification of vesicles and shuts down transcription of the class II transactivator gene as well as de novo biosynthesis of class II-related molecules and DM activity. In these conditions, it is unclear that transduced DO could alter the peptide repertoire. Our Western blot and reverse transcriptase-polymerase chain reaction analyses revealed that human DC derived from blood monocytes express small amounts of DO. Transduction of DOß alone resulted in the accumulation of a small pool of DO in DM⁺ CD63⁺ vesicles and at the plasma membrane of mature DC. The cell-surface increase in class II-associated invariant chain peptide (CLIP)/class II complexes is in line with an inhibitory role of DO on DM. Cotransduction of DO and DOß only slightly increased CLIP and DO levels at the cell surface. Together with the fact that a large fraction of transduced DO remains in the endoplasmic reticulum, this suggests that DM is limiting in these conditions. DO expression did not affect a mixed lymphocyte reaction but reduced presentation of the exogenous gp100 antigen to a specific T cell clone. These results show that transduced DO modulates antigen presentation in human mature MoDC, evoking the possible use of this chaperone for immunotherapy.

Key Words: HLA-DR • HLA-DM • MHC • CLIP • invariant chain

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