Biomedical subjects

K H Western

Publications and source records attributed to K H Western.

3 recordsLinked to original sources

PubMed2001

'Troy-bodies': antibodies as vector proteins for T cell epitopes.

A major objective in vaccine development is the design of reagents that give a strong, specific T cell response. Targeting of antigens to antigen presenting cells (APC) results in enhanced antigen presentation and T cell activation. In this paper, we describe a novel targeting reagent denoted 'Troy-bodies', namely recombinant antibodies with APC-specificity and with T cell epitopes integrated in their C regions. We have made such antibodies with V regions specific for either IgD or MHC class II, and five different T cell epitopes have been tested. All epitopes could be introduced into loops of C domains without disrupting immunoglobulin (Ig) folding. Four have been tested in T cell activation studies, and all could be released and presented by APC. Furthermore, whether IgD- or MHC-specific, the molecules tested enhanced T cell stimulation compared to non-specific control antibodies in vitro as well as in vivo. Using this technology, specific reagents can be designed that target selected antigenic peptides to an APC of choice. Troy-bodies may therefore be useful for manipulation of immune responses, and in particular for vaccination purposes.

Animals↗

PubMed2001

"Troy-bodies": recombinant antibodies that target T cell epitopes to antigen presenting cells.

Targeting of antigens to antigen presenting cells (APC) results in enhanced antigen presentation and T cell activation. In this paper, we describe a novel targeting reagent denoted "Troy-bodies", namely recombinant antibodies with APC-specific V regions and C regions with integrated T cell epitopes. We have made such antibodies with V regions specific for either IgD or MHC class II, and four different T cell epitopes have been tested. All four epitopes could be introduced into loops of C domains without disrupting Ig folding, and they could be released and presented by APC. Furthermore, whether IgD- or MHC-specific, the molecules enhanced T cell stimulation compared to non-specific control antibodies in vitro as well as in vivo. Using this technology, specific reagents can be designed that target selected antigenic peptides to an APC of choice. Troy-bodies may therefore be useful for manipulation of immune responses, and in particular for vaccination purposes.

Animals↗

PubMed2000

Donor neutrophil function after plateletpheresis.

BACKGROUND: Neutrophils are important mediators of inflammation and may be activated by foreign surfaces in apheresis systems. Because most of the WBCs are returned to the donor, it was investigated whether artificial activation leads to altered donor neutrophil function. STUDY DESIGN AND METHODS: Three apheresis systems (Amicus, Autopheresis-C, and CS-3000; all: Baxter Fenwal) were investigated. Preapheresis and postapheresis blood samples were drawn from 10 volunteer donors, with all three apheresis systems used in random order for each donor. Changes in neutrophil phagocytic ability, oxidative burst, and expression of L-selectin and CD11b were measured by flow cytometry, and plasma concentrations of myeloperoxidase and lactoferrin were measured by EIA. Complement activation was evaluated by quantification of C3bc and the terminal complement complex by EIA. RESULTS: Neutrophil expression of L-selectin increased after apheresis (p = 0.02), and the production of oxygen radicals was reduced (p = 0.01). This effect was possibly a result of priming. Complement was not activated. There were no significant differences in neutrophil function after apheresis with any of the three apheresis systems. CONCLUSIONS: Neutrophil function was altered after apheresis, although to a very small extent, and contact between neutrophils and the foreign surface in the apheresis systems is found to be a biotolerant procedure.

Blood Donors↗