Antigen Processing Capacity of Dendritic Cells from Mice of Different MHC Backgrounds: Down-Regulation upon Culture and Evidence for Heterogeneity of Dendritic Cell Populations
Dendritic cells (DC) are highly specialized to initiate primary immune responses.1 They exhibit the necessary properties for this task at different stages of their lifespan. In an immature state, while resident in the tissues, they are very efficient in processing native protein antigens and thus generating MHC class II/peptide ligands for the antigen-specific T cell receptors. After undergoing a maturation process they acquire the adhesion molecules and costimulatory molecules necessary for the powerful stimulation of resting T cells2–4 and they greatly reduce the capacity to process native proteins.5–9 At the cellular level the decrease of processing activity in maturing DC was correlated with the disappearance of acidic, endosomal organelles and with the loss of invariant chain expression (reviewed in1). Furthermore it was shown that biosynthesis of MHC class II and invariant chain molecules is massive at a time when processing activity is high (i.e. in freshly isolated Langerhans cells); upon culture biosynthesis of both molecules is largely shut down (reviewed in1). These cellular and molecular observations may explain the down-regulation of processing.
KeywordsDendritic Cell Mature Dendritic Cell Invariant Chain Primary Immune Response Dendritic Cell Population
Unable to display preview. Download preview PDF.
- 4.U. O’Doherty, R.M. Steinman, M. Peng, P.U. Cameron, S. Gezelter, I. Kopeloff, W.J. Swiggard, M. Pope, and N. Bhardwaj, Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium, J. Exp. Med. 178:1067(1993).PubMedCrossRefGoogle Scholar
- 5.N. Romani, S. Koide, M. Crowley, M. Witmer-Pack, A.M. Livingstone, C.G. Fathman, K. Inaba, and R.M. Steinman, Presentation of exogenous protein antigens by dendritic cells to T cell clones: intact protein is presented best by immature epidermal Langerhans cells. J. Exp. Med. 169:1169 (1989).PubMedCrossRefGoogle Scholar
- 6.E. Pure, K. Inaba, M.T. Crowley, L. Tardelli, M.D. Witmer-Pack, G. Ruberti, G. Fathman, and R.M.Steinman, Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain, J. Exp. Med. 172:1459(1990).PubMedCrossRefGoogle Scholar