Effects of the geometry of the immunological synapse on the delivery of effector molecules

被引:37
作者
Coombs, D [1 ]
Goldstein, B
机构
[1] Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada
[2] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA
关键词
D O I
10.1529/biophysj.104.045674
中图分类号
Q6 [生物物理学];
学科分类号
071011 [生物物理学];
摘要
Recent experiments focusing on the function of the immunological synapse formed between a T cell and an antigen-presenting cell raise many questions about its purpose. We examine the proposal that the close apposition of the cell membranes in the central region of the synapse acts to focus T-cell secretions on the target cell, thus reducing the effect on nearby cells. We show that the efficiency of targeted T-cell responses to closely apposed cells is only weakly dependent on the distance between the cells. We also calculate effective ( diffusion-limited) rates of binding and unbinding for molecules secreted within the synapse. We apply our model to the stimulation of B cells by secreted interleukin-4 (IL-4), and find that very few molecules of IL-4 need be released to essentially saturate the IL-4 receptors on the B-cell surface.
引用
收藏
页码:2215 / 2220
页数:6
相关论文
共 34 条
[1]
ON DIFFUSION-CONTROLLED DISSOCIATION [J].
BERG, OG .
CHEMICAL PHYSICS, 1978, 31 (01) :47-57
[2]
Differential segregation in a cell-cell contact interface:: The dynamics of the immunological synapse [J].
Burroughs, NJ ;
Wülfing, C .
BIOPHYSICAL JOURNAL, 2002, 83 (04) :1784-1796
[3]
Carslaw H. S., 1959, CONDUCTION HEAT SOLI
[4]
Equilibrium thermodynamics of cell-cell adhesion mediated by multiple ligand-receptor pairs [J].
Coombs, D ;
Dembo, M ;
Wofsy, C ;
Goldstein, B .
BIOPHYSICAL JOURNAL, 2004, 86 (03) :1408-1423
[5]
The human natural killer cell immune synapse [J].
Davis, DM ;
Chiu, I ;
Fassett, M ;
Cohen, GB ;
Mandelboim, O ;
Strominger, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15062-15067
[6]
What is the importance of the immunological synapse? [J].
Davis, DM ;
Dustin, ML .
TRENDS IN IMMUNOLOGY, 2004, 25 (06) :323-327
[7]
Information transfer at the immunological synapse [J].
Delon, J ;
Germain, RN .
CURRENT BIOLOGY, 2000, 10 (24) :R923-R933
[8]
Eigen M., 1974, Quantum Statistical Mechanics in the Natural Sciences, P37
[9]
GALIZZI JP, 1989, J BIOL CHEM, V264, P6984
[10]
APPROXIMATING THE EFFECTS OF DIFFUSION ON REVERSIBLE-REACTIONS AT THE CELL-SURFACE - LIGAND-RECEPTOR KINETICS [J].
GOLDSTEIN, B ;
DEMBO, M .
BIOPHYSICAL JOURNAL, 1995, 68 (04) :1222-1230