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The Journal of Membrane Biology

, Volume 252, Issue 4–5, pp 397–412 | Cite as

Membrane Organization and Physical Regulation of Lymphocyte Antigen Receptors: A Biophysicist’s Perspective

  • Laurent LimozinEmail author
  • Pierre-Henri Puech
Article
Part of the following topical collections:
  1. Membrane and Receptor Dynamics

Abstract

Receptors at the membrane of immune cells are the central players of innate and adaptative immunity, providing effective defence mechanisms against pathogens or cancer cells. Their function is intimately linked to their position at and within the membrane which provides accessibility, mobility as well as membrane proximal cytoskeleton anchoring, all of these elements playing important roles in the final function and links to cellular actions. Understanding how immune cells integrate the specific signals received at their membrane to take a decision remains an immense challenge and a very active field of fundamental and applied research. Recent progress in imaging and micromanipulation techniques have led to an unprecedented refinement in the description of molecular structures and supramolecular assemblies at the immune cell membrane, and provided a glimpse into their dynamics and regulation by force. Several key elements have been scrutinized such as the roles of relative sizes of molecules, lateral organisation, motion in the membrane of the receptors, but also physical cues such as forces, mediated by cellular substrates of different rigidities or applied by the cell itself, in conjunction with its partner cell. We review here these recent discoveries associated with a description of the biophysical methods used. While a conclusive picture integrating all of these components is still lacking, mainly due to the implication of diverse and different mechanisms and spatio-temporal scales involved, the amount of quantitative data available opens the way for physical modelling and numerical simulations and new avenues for experimental research.

Keywords

Immunobiophysics Lymphocyte Cell adhesion mechanisms Receptors Mechanobiology 

Abbreviations

AFM

Atomic force microscopy

APC

Antigen presenting cell

BCR

B cell receptor

BFP

Bio-membrane force probe

CAR

Chimeric antigen receptor

CDR

Complementary determining regions

FcR

Constant fragment receptor

FCS

Fluorescence correlation microscopy

FRAP

Fluorescence recovery after photobleaching

FRET

Förster resonance energy transfer

ICAM

Inter-cellular adhesion molecule

Ig

Immunoglobulin

ITAM

Immuno-receptor tyrosine-based activation motifs

ITIM

Immuno-receptor tyrosine-based inhibition motifs

LFA-1

Lymphocyte function-associated antigen 1

LFC

Laminar flow chamber

NK

Natural killer

pMHC

peptide Major histocompatibility complex

RICM

Reflection interference contrast microscopy

SIM

Structured illumination microscopy

SMLM

Single-molecule localisation microscopy

TCR

T-cell receptor

TFM

Traction force microscopy

TIRF

Total internal reflection fluorescence

Notes

Acknowledgements

We thank Pierre Dillard and Fuwei Pi for the microscopy images of Fig. 2b, Pierre Bongrand and Kheya Sengupta for scientific exchanges and critical reading of the manuscript, as well as all present and past members of Laboratoire Adhesion and Inflammation for numerous discussions.

Compliance with Ethical Standards

Conflict of interest

Authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Aix Marseille Univ, CNRS, INSERM, Laboratoire Adhesion and InflammationMarseilleFrance

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