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001-es BibID:BIBFORM020768
Első szerző:Roszik János (biofizikus)
Cím:T-cell synapse formation depends on antigen recognition but not CD3 interaction : studies with TCR : zeta, a candidate transgene for TCR gene therapy / Roszik J., Sebestyén Z., Govers C., Guri Y., Szöor A., Pályi-Krekk Z., Vereb G., Nagy P., Szöllosi J., Debets R.
Dátum:2011
Megjegyzések:T-cell receptors (TCRs) can be genetically modified to improve gene-engineered T-cell responses, a strategy considered critical for the success of clinical TCR gene therapy to treat cancers. TCR:zeta, which is a heterodimer of TCRalpha and beta chains each coupled to complete human CD3zeta, overcomes issues of mis-pairing with endogenous TCR chains, shows high surface expression and mediates antigen-specific T-cell functions in vitro. In the current study, we further characterized TCR:zeta in gene-engineered T cells and assessed whether this receptor is able to interact with surface molecules and drive correct synapse formation in Jurkat T cells. The results showed that TCR:zeta mediates the formation of synaptic areas with antigen-positive target cells, interacts closely with CD8alpha and MHC class I (MHCI), and co-localizes with CD28, CD45 and lipid rafts, similar to WT TCR. TCR:zeta did not closely associate with endogenous CD3epsilon, despite its co-presence in immune synapses, and TCR:zeta showed enhanced synaptic accumulation in T cells negative for surface-expressed TCR molecules. Notably, synaptic TCR:zeta demonstrated lowered densities when compared with TCR in dual TCR T cells, a phenomenon that was related to both extracellular and intracellular CD3zeta domains present in the TCR:zeta molecule and responsible for enlarged synapse areas
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adoptive Transfer
Antigens
Antigens,CD28
Antigens,CD3
Antigens,CD45
Antigens,CD8
article
Biophysics
Cells
Flow Cytometry
Gene Therapy
genetics
Histocompatibility Antigens
Histocompatibility Antigens Class I
Human
Humans
Hungary
Immunity,Cellular
Immunological Synapses
immunology
In Vitro
Jurkat Cells
lipid raft
LIPID RAFTS
Membrane Microdomains
metabolism
physiology
Receptor-CD3 Complex,Antigen,T-Cell
Receptors,Antigen,T-Cell,alpha-beta
Research
Research Support
Support
Synapses
T-Lymphocytes
therapy
Transgenes
Megjelenés:European Journal of Immunology. - 41 : 5 (2011), p. 1288-1297. -
További szerzők:Sebestyén Zsolt Govers, Coen Guri, Yakir Szöőr Árpád (1984-) (orvos) Pályiné Krekk Zsuzsanna (1974-) (molekuláris biológus) Vereb György (1965-) (biofizikus, orvos) Nagy Péter (1971-) (biofizikus) Szöllősi János (1953-) (biofizikus) Debets, Reno
Internet cím:DOI
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