A model for the interplay of receptor recycling and receptor-mediated contact in T cells.
Orientation of organelles inside T cells (TC) toward antigen-presenting cells (APC) ensures that the immune response is properly directed, but the orientation mechanisms remain largely unknown. Structural dynamics of TC are coupled to dynamics of T-cell receptor (TCR), which recognizes antigen on the APC surface. Engagement of the TCR triggers its internalization followed by delayed polarized recycling to the plasma membrane through the submembrane recycling compartment (RC), which organelle shares intracellular location with the TC effector apparatus. TCR engagement also triggers TC-APC interface expansion enabling further receptor engagement. To analyze the interplay of the cell-cell contact and receptor dynamics, we constructed a new numerical model. The new model displays the experimentally observed selective stabilization of the contact initiated next to the RC, and only transient formation of contact diametrically opposed to the RC. In the general case wherein the TC-APC contact is initiated in an arbitrary orientation to the RC, the modeling predicts that the contact dynamics and receptor recycling can interact, resulting effectively in migration of the contact to the TC surface domain adjacent to the submembrane RC. Using three-dimensional live-cell confocal microscopy, we obtain data consistent with this unexpected behavior. We conclude that a TC can stabilize its contact with an APC by aligning it with the polarized intracellular traffic of TCR. The results also suggest that the orientation of TC organelles, such as the RC and the effector apparatus, toward the APC can be achieved without any intracellular translocation of the organelles.
Arkhipov
Sergey N
SN
Department of Computational Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Maly
Ivan V
IV
D000938:Antigen-Presenting Cells / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D018613:Microscopy, Confocal; D018448:Models, Immunological; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell