NDLI: Solid Phase Matrices: Cell-Free Micro-Platform for T Cell Recruitment and Stimulation

Content Provider	IEEE Xplore Digital Library
Author	Kokaji, A.I. Kane, K.P.
Copyright Year	2004
Description	Author affiliation: University of Alberta (Kokaji, A.I.)
Abstract	Optimal stimulation of antigen specific T cells requires that peptide antigens bound by class I and class II major histocompatibility complex molecules (MHC) are displayed, in conjunction with a variety of costimulatory ligands, on a large surface approximating that of a cell. We have incorporated these principles in the design of cell-free artificial antigen presenting cell surfaces (solid phase matrices, SPMs) constructed on 5 micron latex beads for use in ex vivo T cell stimulation for adoptive immunotherapy and as platforms for T cell vaccines. We demonstrate that naturally expressed or recombinant peptide-MHC complexes and costimulator molecules can be immobilized and displayed simultaneously on the surface of SPMs. Eight or more distinct costimulatory molecules or ligands can be presented on SPMs at physiological densities and the relative density of each ligand can be varied in a precise and independent manner. This allows for control of the contribution of individual ligands relative to others, with the possibility of altering the type of resulting T cell response. The ligands that can be presented on the SPMs include among others: human or mouse class I and class II MHC peptide complexes (antigen specific T cell receptor ligands), B7-1 and 2 (CD28 ligands), 4-1BBL (TNF family costimulator), ICAM-1 (LFA-1 adhesion ligand), CD1d (NKT cell ligand), MICA and Rae-1 antigens (NKG2D costimulatory ligands). All of the immobilized ligands retain their native conformations, since recognition by conformation dependent antibodies is indicated by FACS analysis of the SPMs. Recently, it has been shown that IL-15 receptor alpha (α) can bind the IL-15 cytokine with high affinity and present IL-15 on antigen presenting cells in trans to T cells for stimulation. We are able to display IL-15Rα bound with IL-15 on the SPMs, in addition to peptide-MHC complexes and costimulator ligands to aid T cell responsiveness. We are presently examining the ligand requirements for optimal stimulation of na��ve and effector/memory T cell subsets. We have found that IL-15Rα bound and presented on the SPM has a rapid and profound effect on the recruitment and binding of T cells to the SPMs. Within 2-4 hours, T cells bind avidly to the SPMs bearing the IL-15Rα-IL-15 complex. The ability of the IL-15R-IL-15 complex to recruit T cells to the SPMs may provide improvement to the utility of SPMs as vaccine vehicles, allowing the attraction of T cells to the SPMs displaying T cell antigens and costimulators, despite the non-motile nature of SPMs.
Starting Page	563
Ending Page	563
File Size	34525
Page Count	1
File Format	PDF
ISBN	0769521894
DOI	10.1109/ICMENS.2004.1509011
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2004-08-25
Publisher Place	Canada
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Solids Recruitment Scanning probe microscopy Peptides Vaccines Immune system Humans Mice Adhesives Displays
Content Type	Text
Resource Type	Article

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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