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Recently, I proposed a novel biophysical mechanisms
for NK cell-mediated recognition (see Abstract of paper).
This model does not assume the presence of the specific
positive receptors NK-receptor(s) on the NK cells and
corresponding ligand(s) (counter-receptor(s)) on the TCs.
Many receptor and counter-receptor pairs (i.g. ICAM1,2,3
-LFA-1, CD2-LFA-3, etc.) pre-exist on
the NK-like cells and the NK cell could transfer these
molecules by the vesicules to NK-sensetive target cells.
This "Harpooning" mechanism of binding of the TC by NK
cell causing the TC to become sencetive to lysis by
NK cell.
I would like to collaborate with somebody who will be
interested in join exp. and theor. developing of
this model.
I will be very grateful if anybody send me data on
transferring of glycoproteins, gagliosides, lipids from
killer cells to TCs.
I will be happy to send copy of my paper to whom it
may be concern.
Sincerely Yours
Vladimir Kuznetsov
----------------
V. A.Kuznetsov, Ph.D., Sci. D.
Lab. of Molec. Tumor Biology
Div. of Cellular and Gene Therapies
CBER/FDA,
Bldg.29B, Rm. 2G07, Bethesda, 20892, MD,
U.S.A.
tel: 301 827-0699, FAX: 301 827-0449
e-mails: kuznetsov@a1.cber.fda.gov
kuznetso@helix.nih.gov
Vladimir A. KUZNETSOV
''Harpoon'' Model for Cell-Cell Adhesion and Recognition
Target Cells by the Natural Killer Cells.(1996). J. Theor. Biol.
108, 321-342.
Laboratory of Molecular Tumor Biology,
Center for Biologics Evaluation and Research
Food and Drug Administration
Bethesda, MD, 20895, USA
e-mail: kuznetsov@a1.cber.fda.gov
ABSTRACT
The mechanism of recognition by natural killer (NK) cells is still
unknown. A dynamical model is formulated describing recognition of
NK-sensitive target cells (TCs) by NK cells or NK-like cells. This
model does not assume the presence of the specific NK-receptor(s) on
the membrane of NK cells and corresponding specific ligands on the
NK-sensitive TCs. We suggest: 1) the expression of various kinds
of "non-NK receptors" and corresponding ligands
(counter-receptors) on the plasma membrane of the same NK cell and,
possibly, of TCs (for instance: LFA-1 and ICAM-1-ICAM3, CD2 and
LFA-3; receptors for TNF and corresponding ligand etc.), 2) the
presence of multiple disorders in the organization of
`extracellular matrix - surface membrane - submembrane
cytoskeleton' assembly
of the NK-sensitive TCs; 3) nonspecific primary linking of NK
cell with TCs, which induces a transfer of vesicles or membrane
fragments from the NK surface to the target cell surface (and
perhaps vice versa). These processes may also permit transfer
many types
of receptor and counter-receptor molecules from the surface of one
of the conjugated cell to the other by vesicles or membrane
fragments. After transferral through intercellular cleft,
the free receptors and counter-receptors will be localized on both
cell surfaces at the contact region between conjugated cells. By
these model the NK cell can `harpoon' TC and enhance the binding
forces between cells up to the critical level and then switch on
killing mechanisms for the TC. By means of this "harpoon" model of
cell recognition, it seems possible to explain the nature of the
wide polymorphism of TCs which are sensitive to the effect of NK
and NK-like cells. A mathematical model of the NK cell cytotoxic
reaction is described. The model describes many nonlinear
peculiarities of the cytotoxic process and predicts some new
phenomena. We suggest new approaches of manipulation of cell
membranes which can transform NK-resistant target cells in NK
sensitive cells and the vice versa.
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