Increased TCR Avidity after T Cell Activation

Fahmy, Tarek M.; Bieler, Joan Glick; Edidin, Michael; Schneck, Jonathan P.

doi:10.1016/s1074-7613(01)00096-6

Cited by 101 publications

(59 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1A and B ) and quantified their absolute numbers and characteristics. T cells stimulated with T102L accumulated more TCR microclusters on average (17) than cells stimulated with the control self peptide β-2m (10) ( Fig. 3B ).…”

Section: Resultsmentioning

confidence: 99%

TCR Microclusters Pre-Exist and Contain Molecules Necessary for TCR Signal Transduction

Crites

Padhan

Muller

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

TCR-dependent signaling events have been observed to occur in TCR microclusters. We found that some TCR microclusters are present in unstimulated murine T cells, indicating that the mechanisms leading to microcluster formation do not require ligand binding. These preexisting microclusters increase in absolute number following engagement by low-potency ligands. This increase is accompanied by an increase in cell spreading, with the result that the density of TCR microclusters on the surface of the T cell is not a strong function of ligand potency. In characterizing their composition, we observed a constant number of TCRs in a microcluster, constitutive exclusion of the phosphatase CD45, and preassociation with the signaling adapters LAT and Grb2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could in part explain the rapid kinetics with which TCR signal transduction occurs.

show abstract

Section: Resultsmentioning

confidence: 99%

TCR Microclusters Pre-Exist and Contain Molecules Necessary for TCR Signal Transduction

Crites

Padhan

Muller

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The geometry of the nanobead, such as high local curvature at the interface, may preclude multiple productive receptor-ligand interactions. Alternatively, nanoscale platforms may preferentially interact with nano-clustered receptors such as the TCR [44,45]. Nanoscale bead-cell interaction platforms thus represent not just a novel approach to immunotherapy, but a tool for studying the delivery of biological signals at the cell membrane [19].…”

Section: Discussionmentioning

confidence: 99%

Nanoscale artificial antigen presenting cells for T cell immunotherapy

Perica

Medero

Durai

et al. 2014

Nanomedicine: Nanotechnology, Biology and Medicine

Self Cite

114

128

View full text Add to dashboard Cite

Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for both adoptive and active immunotherapy. Thus far, aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to micron-sized beads. Nanoscale platforms have different trafficking and biophysical interaction properties and may allow development of new immunotherapeutic strategies. We therefore manufactured aAPC based on two types of nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles (50–100 nm in diameter) and avidin-coated quantum dot nanocrystals, (~30 nm). Nanoscale aAPC induced antigen-specific T cell proliferation from mouse splenocytes and human peripheral blood T cells. When injected in vivo, both iron-dextran particles and quantum dot nanocrystals enhanced tumor rejection in a subcutaneous mouse melanoma model. This is the first description of nanoscale aAPC that induce antigen-specific T cell proliferation in vitro and lead to effective T cell stimulation and inhibition of tumor growth in vivo.

show abstract

“…T cell affinity refers to the binding strength of a single TCR and peptide-major histocompatibility complex (pMHC) interaction, whereas T cell avidity integrates interactions between multiple TCRs and coreceptors with pMHC molecules (van den Berg and Rand, 2007). TCR clustering and colocalization with coreceptors upon T cell activation can also affect T cell avidity (Demotte et al, 2008; Fahmy et al, 2001). The fluorescence intensity of T cells stained with pMHC multimers has been used as a proxy for the affinity and/or avidity of endogenous T cell populations, because pMHC multimer binding intensity has correlated with functional assays of T cell avidity (Crawford et al, 1998; Falta et al, 2005; Wang and Altman, 2003; Yee et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance

et al. 2018

View full text Add to dashboard Cite

SUMMARY Mechanisms implicated in robust transplantation tolerance at the cellular level can be broadly categorized into those that inhibit alloreactive T cells intrinsically (clonal deletion and dysfunction) or extrinsically through regulation. Here, we investigated whether additional population-level mechanisms control T cells by examining whether therapeutically induced peripheral transplantation tolerance could influence T cell populations’ avidity for alloantigens. Whereas T cells with high avidity preferentially accumulated during acute rejection of allografts, the alloreactive T cells in tolerant recipients retained a low-avidity profile, comparable to naive mice despite evidence of activation. These contrasting avidity profiles upon productive versus tolerogenic stimulation were durable and persisted upon alloantigen reencounter in the absence of any immunosuppression. Thus, peripheral transplantation tolerance involves control of alloreactive T cells at the population level, in addition to the individual cell level. Controlling expansion or eliminating high-affinity, donorspecific T cells long term may be desirable to achieve robust transplantation tolerance in the clinic.

show abstract

Increased TCR Avidity after T Cell Activation

Cited by 101 publications

References 48 publications

TCR Microclusters Pre-Exist and Contain Molecules Necessary for TCR Signal Transduction

TCR Microclusters Pre-Exist and Contain Molecules Necessary for TCR Signal Transduction

Nanoscale artificial antigen presenting cells for T cell immunotherapy

Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance

Contact Info

Product

Resources

About