Distinct Dendritic Cell Populations Sequentially Present Antigen to CD4 T Cells and Stimulate Different Aspects of Cell-Mediated Immunity (original) (raw)

The mode of protein antigen administration determines preferential presentation of peptide-class II complexes by lymph node dendritic or B cells

International Immunology, 1997

complexes following administration of protein in adjuvant or in soluble form. Three different antigen-presenting cell (APC) populations were separated from draining lymph node cells from mice immunized s.c. with hen egg-white lysozyme (HEL) in adjuvant or with adjuvant only followed by soluble HEL: DC (N418 ⍣ , class II ⍣ , B220 -, low buoyant density), large B cells (B220 ⍣ , low buoyant density) and small B cells (B220 ⍣ , high buoyant density). HEL peptide-class II complexes displayed by these APC were evaluated by their capacity to activate HEL-specific T hybridoma cells. Following immunization with HEL in adjuvant, DC are the only lymph node APC population expressing detectable HEL peptide-class II complexes. Conversely, after i.v. administration of soluble HEL in mice previously injected with adjuvant only, lymph node B cells are much more efficient than DC in presenting peptide-class II complexes to T cells. Therefore, different modes of protein antigen administration lead to selective expression of antigenic complexes by different APC populations. These data correlate with the observation that, unlike B cells, DC recruited in lymph nodes of mice injected with adjuvant only present in vitro processed protein antigen much less efficiently than synthetic peptides, probably as a consequence of their maturation in vivo.

Dendritic cells but not B cells present antigenic complexes to class II- restricted T cells after administration of protein in adjuvant

Journal of Experimental Medicine, 1996

We have analyzed the relative contribution of dendritic cells (DC) and B cells in the presentation of peptide--class II complexes in an inflammatory situation in vivo. Draining lymph node cells from mice immunized subcutaneously with hen egg-white lysozyme (HEL) in adjuvant display HEL peptide-major histocompatibility complex class II complexes able to stimulate, in the absence of any further antigen addition, specific T hybridoma cells. The antigen-presenting capacity of three different antigen-presenting cell (APC) populations recruited in lymph nodes, DC (N418 +, class II +, B220-, low buoyant density), large B cells (B220 +, low buoyant density), and small B cells (B220 +, high buoyant density), was analyzed. After immunization with HEL in adjuvant, DC are the only lymph node APC population expressing detectable HEL peptide-class II complexes. These results indicate that lymph node DC and not B cells are the APC initiating the immune response in vivo after administration of antigen in adjuvant.

Efficient Presentation of Phagocytosed Cellular Fragments on the Major Histocompatibility Complex Class II Products of Dendritic Cells

Journal of Experimental Medicine, 1998

Cells from the bone marrow can present peptides that are derived from tumors, transplants, and self-tissues. Here we describe how dendritic cells (DCs) process phagocytosed cell fragments onto major histocompatibility complex (MHC) class II products with unusual efficacy. This was monitored with the Y-Ae monoclonal antibody that is specific for complexes of I-A b MHC class II presenting a peptide derived from I-E ␣ . When immature DCs from I-A b mice were cultured for 5-20 h with activated I-E ϩ B blasts, either necrotic or apoptotic, the DCs produced the epitope recognized by the Y-Ae monoclonal antibody and stimulated T cells reactive with the same MHC-peptide complex. Antigen transfer was also observed with human cells, where human histocompatibility leukocyte antigen (HLA)-DR ␣ includes the same peptide sequence as mouse I-E ␣ . Antigen transfer was preceded by uptake of B cell fragments into MHC class II-rich compartments. Quantitation of the amount of I-E protein in the B cell fragments revealed that phagocytosed I-E was 1-10 thousand times more efficient in generating MHC-peptide complexes than preprocessed I-E peptide. When we injected different I-Ebearing cells into C57BL/6 mice to look for a similar phenomenon in vivo, we found that short-lived migrating DCs could be processed by most of the recipient DCs in the lymph node. The consequence of antigen transfer from migratory DCs to lymph node DCs is not yet known, but we suggest that in the steady state, i.e., in the absence of stimuli for DC maturation, this transfer leads to peripheral tolerance of the T cell repertoire to self.

Extracellular antigen processing and presentation by immature dendritic cells

Proceedings of the National Academy of Sciences, 1999

In antigen presentation to CD4 ؉ T cells, proteins are degraded to peptide fragments and loaded onto class II MHC molecules in a process involving the peptide exchange factors H-2M (murine) or HLA-DM (human). In many antigen-presenting cells these processes occur in intracellular endosomal compartments, where peptides are generated and loaded onto class II MHC proteins for subsequent transport to the surface and presentation to T cells. Here, we provide evidence for an additional antigen-processing pathway in immature dendritic cells (DC). Immature DC express at the cell surface empty or peptide-receptive class II MHC molecules, as well as H-2M or HLA-DM. Secreted DC proteases act extracellularly to process intact proteins into antigenic peptides. Peptides produced by such activity are efficiently loaded onto cell surface class II MHC molecules. Together these elements comprise an unusual extracellular presentation pathway in which antigen processing and peptide loading can occur entirely outside of the cell.