Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Antigen presentation is a key rate-limiting step in the immune response. Dendritic cells (DC) are the most potent antigen-presenting cells for naive T cells, due to their high expression of MHC and co-stimulatory molecules, but little is known about the biochemical pathways that regulate this function. We here demonstrate that monocyte-derived mature DC can be infected with adenovirus at high efficiency (>95%) and that this procedure can be used to dissect out which pathways are essential for inducing DC antigen presentation to naive T cells. Using adenoviral transfer of the endogenous inhibitor of NF-kappaB, IkappaBalpha, we show that DC antigen presentation is NF-kappaB dependent. The mechanism for this is that NF-kappaB is essential for three aspects of antigen-presenting function: blocking NF-kappaB coordinately down-regulates HLA class II, co-stimulatory molecules like CD80, CD86 and CD40, and immuno-stimulatory cytokines like IL-12 and tumor necrosis factor-alpha. In contrast adhesion molecules are up-regulated after infection with the adenovirus transferring IkappaBalpha, indicating that NF-kappaB also regulates the duration of T cell-DC interaction. These results establish NF-kappaB as an effective target for blocking DC antigen presentation and inhibiting T cell-dependent immune responses, and this finding has potential implications for the development of therapeutic agents for use in allergy, autoimmunity and transplantation.

Original publication

DOI

10.1093/intimm/13.5.675

Type

Journal article

Journal

Int Immunol

Publication Date

05/2001

Volume

13

Pages

675 - 683

Keywords

Adenoviridae, Antigen Presentation, Antigens, CD, B7-1 Antigen, B7-2 Antigen, CD40 Antigens, Cytokines, DNA-Binding Proteins, Dendritic Cells, Genetic Vectors, Histocompatibility Antigens Class II, Humans, I-kappa B Proteins, In Vitro Techniques, Membrane Glycoproteins, NF-KappaB Inhibitor alpha, NF-kappa B