Biomedical subjects

Arnold H Bakker

Publications and source records attributed to Arnold H Bakker.

4 recordsLinked to original sources

PubMed2005

MHC multimer technology: current status and future prospects.

The detection of antigen-specific T cell responses by MHC multimer staining is rapidly becoming one of the core immunological techniques, and the technology to produce MHC multimers has been optimized substantially in recent years. Furthermore, recent work demonstrates the potential of high-throughput detection of T cell responses and suggests that manipulation of T cell responses through the use of multimeric MHC reagents is also feasible.

Animals↗

PubMed2004

Antigen bias in T cell cross-priming.

Activated CD8+ T cells detect virally infected cells and tumor cells by recognition of major histocompatibility complex class I-bound peptides derived from degraded, endogenously produced proteins. In contrast, CD8+ T cell activation often occurs through interaction with specialized antigen-presenting cells displaying peptides acquired from an exogenous cellular source, a process termed cross-priming. Here, we observed a marked inefficiency in exogenous presentation of epitopes derived from signal sequences in mouse models. These data indicate that certain virus- and tumor-associated antigens may not be detected by CD8+ T cells because of impaired cross-priming. Such differences in the ability to cross-present antigens should form important considerations in vaccine design.

Animals↗

PubMed2002

Analysis of protease activity in live antigen-presenting cells shows regulation of the phagosomal proteolytic contents during dendritic cell activation.

Here, we describe a new approach designed to monitor the proteolytic activity of maturing phagosomes in live antigen-presenting cells. We find that an ingested particle sequentially encounters distinct protease activities during phagosomal maturation. Incorporation of active proteases into the phagosome of the macrophage cell line J774 indicates that phagosome maturation involves progressive fusion with early and late endocytic compartments. In contrast, phagosome biogenesis in bone marrow-derived dendritic cells (DCs) and macrophages preferentially involves endocytic compartments enriched in cathepsin S. Kinetics of phagosomal maturation is faster in macrophages than in DCs. Furthermore, the delivery of active proteases to the phagosome is significantly reduced after the activation of DCs with lipopolysaccharide. This observation is in agreement with the notion that DCs prevent the premature destruction of antigenic determinants to optimize T cell activation. Phagosomal maturation is therefore a tightly regulated process that varies according to the type and differentiation stage of the phagocyte.

Animals↗

PubMed2002

A closer look at proteolysis and MHC-class-II-restricted antigen presentation.

Antigen presentation by MHC class II molecules relies on the action of endocytic proteases, which are differentially expressed in antigen-presenting cells and are regulated by different components of the immune system. Endocytic enzymes process and convert exogenous antigens into peptidic determinants capable of interaction with MHC class II molecules. Chemical and genetic tools have recently been developed to study the role of lysosomal proteases in antigen presentation.

Animals↗