Correlation of a dynamic model for immunological synapse formation with effector functions: two pathways to synapse formation

Lee, Sung-Joo E.; Hori, Yûko; Groves, Jay T.; Dustin, Michael L.; Chakraborty, Arup K.

doi:10.1016/s1471-4906(02)02285-8

Cited by 59 publications

(44 citation statements)

References 57 publications

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“…One pathway is antigen independent through a ring junction (CTLs in inflamed sites) and one pathway is antigen dependent through a nascent IS (helper T cells). Recently, a computational model also suggested fundamental differences between helper T cell and CTL IS formation that are consistent with our data (41). The ring junction of the CTL may constitute a specific functional structure that could be described as a "presynapse."…”

Section: Discussionsupporting

confidence: 89%

Cytotoxic T lymphocytes form an antigen-independent ring junction

Somersalo¹,

Anikeeva²,

Sims³

et al. 2004

J. Clin. Invest.

114

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Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: MHC-peptide (MHCp); immunological synapse (IS); lymphocyte function associated antigen-1 (LFA-1); peripheral supramolecular activation cluster (pSMAC); T cell receptor (TCR); central supramolecular activation cluster (cSMAC); glycophosphatidylinositol (GPI); 6-histidine-tagged (His6).

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Section: Discussionsupporting

confidence: 89%

Cytotoxic T lymphocytes form an antigen-independent ring junction

Somersalo¹,

Anikeeva²,

Sims³

et al. 2004

J. Clin. Invest.

114

View full text Add to dashboard Cite

show abstract

“…This sort of protein reorganization is also different from proposed mechanisms of T cell immunological synapse formation that rely on a dynamic equilibrium between molecular binding and unbinding (37)(38)(39). However, the mechanical effects uncovered here are quite general.…”

Section: Discussioncontrasting

confidence: 56%

Protein patterns at lipid bilayer junctions

Parthasarathy

Groves

2004

Proc. Natl. Acad. Sci. U.S.A.

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We introduce a simple intermembrane junction system in which to explore pattern and structure formation by membrane-bound proteins. The junction consists of a planar lipid bilayer to which one species of protein (an IgG antibody) is bound, forming a 2D, compressible fluid. Upon the adhesion of a second lipid bilayer, the formerly uniformly distributed proteins rapidly reorganize into patterns of dense and sparse zones. Using a combination of complementary imaging techniques (fluorescence microscopy, fluorescence interference contrast microscopy, and fluorescence resonance energy transfer), we reconstruct the 3D structure of these intermembrane patterns with nanometer-scale topographic resolution, revealing the orientation of the proteins. The patterns form as the rapid bilayer-bilayer adhesion, often radiating outward from an initial, circular contact site, pushes aside the antibodies, sweeping them into areas of high density and clearing low-density regions. Coarsening of these local features is energetically costly and therefore kinetically trapped; the patterns do not change over tens of minutes. These studies demonstrate that membrane mechanical forces alone, i.e., in the absence of specific biochemical interactions, can drive m-scale organization of membrane proteins.

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“…Our results are consistent with past reports that establish the human CD47-SIRP␣ interaction (6,20,21,23), but the data here show that human versus mouse interactions are biochemically distinct. Differences in affinity could influence downstream signaling, which is clear in other synapses, such as the immunological synapse between T cells and antigen-presenting cells (44) and also in the B cell synapse (45).…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Divergence of CD47 Interactions with Human Signal Regulatory Protein α Reveals Locus of Species Specificity

Subramanian

Boder

Discher

2007

Journal of Biological Chemistry

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Cell-cell interactions between ubiquitously expressed integrinassociated protein (CD47) and its counterreceptor signal regulatory protein (SIRP␣) on phagocytes regulate a wide range of adhesive signaling processes, including the inhibition of phagocytosis as documented in mice. We show that CD47-SIRP␣ binding interactions are different between mice and humans, and we exploit phylogenetic divergence to identify the species-specific binding locus on the immunoglobulin domain of human CD47. All of the studies are conducted in the physiological context of membrane protein display on Chinese hamster ovary (CHO) cells. Novel quantitative flow cytometry analyses with CD47-green fluorescent protein and soluble human SIRP␣ as a probe show that neither human CD47 nor SIRP␣ requires glycosylation for interaction. Human CD47-expressing CHO cells spread rapidly on SIRP␣-coated glass surfaces, correlating well with the spreading of primary human T cells. In contrast, CHO cells expressing mouse CD47 spread minimally and show equally weak binding to soluble human SIRP␣. Further phylogenetic analyses and multisite substitutions of the CD47 Ig domain show that human to cow mutation of a cluster of seven residues on adjacent strands near the middle of the domain decreases the association constant for human SIRP␣ to about onethird that of human CD47. Direct tests of cell-cell adhesion between human monocytes and CD47-displaying CHO cells affirm the species specificity as well as the importance of the newly identified binding locus in cell-cell interactions.Cell-cell interactions are of course critical in immune function but can have important and revealing differences between species as well as nonlinear dependences on molecular parameters, such as affinity. We explore such general issues with integrin-associated protein (IAP), 2 or CD47, which is a ubiquitous but unique immunoglobulin superfamily receptor with a single Ig domain, a pentaspan transmembrane segment, and a variably spliced cytoplasmic tail (1). The known functional roles of CD47, originally limited to integrin activation (2), have expanded considerably since the identification of SIRP␣ as a physiological ligand (3-6). SIRP␣ is another Ig superfamily member with three Ig domains and a single span transmembrane segment. SIRP␣ is also broadly expressed, present at high levels on myeloid lineages (monocytes, neutrophils) and neurons but absent from many if not most other cells (7). Both CD47 and SIRP␣ are found in many mammals, but the differences in sequence (Fig. 1A) across species have yet to be evaluated. CD47-SIRP␣ interactions regulate transmigration of monocytes and neutrophils (8 -11) with severe impairment in neutrophil recruitment to sites of infection in CD47 knock-out mice (12). CD47 on "self " red cells, platelets, lymphocytes, and other nonapoptotic cells inhibits clearance by macrophages in mice by signaling through SIRP␣ (13-16). However, in humans as opposed to mice, severe reductions of CD47 levels on red cells, as found on various Rh-deficient patient ...

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Correlation of a dynamic model for immunological synapse formation with effector functions: two pathways to synapse formation

Cited by 59 publications

References 57 publications

Cytotoxic T lymphocytes form an antigen-independent ring junction

Cytotoxic T lymphocytes form an antigen-independent ring junction

Protein patterns at lipid bilayer junctions

Phylogenetic Divergence of CD47 Interactions with Human Signal Regulatory Protein α Reveals Locus of Species Specificity

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