An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells.

Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells

The anomalous Higgs-top couplings in the MSSM

The anomalous couplings of the top quark and the Higgs boson has been studied in an effective theory resulting in the framework of the minimal supersymmetric extension of the standard model (MSSM) when the heavy fields are integrated out. Constraints on the parameters of the model from the experimental data on the ratio $R_b={\Gamma(Z\to b\bar{b})/\Gamma(Z\to hadrons)}$ are derived.Comment: Latex, 26 pages + 13 ps figures, final version in PR

X-ray line spectrometry in experiments with the aluminium Z-pinch

X-ray line spectrometry with temporal resolution was developed for registration of [He]- and [H]-like aluminium ions spectrum. It was chosen a scheme with scintillator converting X-ray spectrum into the visible image, which was transferred through the flexible optical fiber to the entrance slit of the streak camera. In Z-pinch experiment on the high current S-300 generator the aluminium line spectrum was registered with nanosecond time resolution. The simultaneous appearance of [He]- and [H]-like aluminium ions radiation was observed, that is the evidence of high electron temperature existence in the plasma for a long time before the main part of the load mass comes to the axis. The noticeably changing of radiating plasma parameters was found after the computer treatment of line spectra: the electron concentration is varied in five times ((3…14)×10^19 cm^-3), electron temperature in three times (0.3…1 keV), ion temperature in five times (20…100 keV), – during 50 ns. The great difference between the electron and ion temperature holds during all radiation time and demonstrates the ineffective energy transfer from the kinetic energy of ions to electron.Разработана методика для регистрации с временным разрешением рентгеновских линий [He]- и [H]-подобных ионов алюминия. Рентгеновский спектр преобразовывался с помощью сцинтиллятора в видимое изображение, которое переносилось гибким световодом на входную щель электронно-оптического преобразователя. Регистрация спектра проводилась с наносекундным разрешением в экспериментах с Z-пинчем на сильноточном генераторе С-300. Наблюдалось одновременное появление линий [He]- и [H]-подобных ионов алюминия, что является свидетельством наличия высокой электронной температуры в плазме задолго до момента прихода к оси основной массы Z-пинча. Компьютерная обработка спектров выявила значительные изменения параметров плазмы в процессе сжатия: концентрации в пять раз ((3…14)×10^19 см^-3), электронной температуры в три (0.3…1 кэВ), ионной температуры в пять раз (20…100 кэВ) – за 50 нс. Большой разрыв между ионной и электронной температурами демонстрирует неэффективность передачи энергии от ионов к электронам.Розроблено методику для реєстрації з часовим дозволом рентгенівських ліній [He]- і [H]-подібних іонів алюмінію. Рентгенівський спектр перетворювався за допомогою сцинтиллятора у видиме зображення, що переносилося гнучким світловодом на вхідну щілину електронно-оптичного перетворювача. Реєстрація спектра проводилася з наносекундним дозволом в експериментах з Z-пінчем на потужнострумовому генераторі С-300. Спостерігалася одночасна поява ліній [He]- і [H]-подібних іонів алюмінію, що є свідченням наявності високої електронної температури в плазмі задовго до моменту приходу до осі основної маси Z-пінча. Комп'ютерна обробка спектрів виявила значні зміни параметрів плазми в процесі стиску: концентрації в п'ять разів ((3...14)×10^19см^-3), електронної температури в три (0.3...1кеВ), іонної температури в п'ять разів (20...100 кеВ) – за 50 нс. Великий розрив між іонною й електронною температурами демонструє неефективність передачі енергії від іонів до електронів

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

We report a high precision measurement of the transverse single spin asymmetry $A_N$ at the center of mass energy $\sqrt{s}=200$ GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The $A_N$ was measured in the four-momentum transfer squared $t$ range $0.003 \leqslant |t| \leqslant 0.035$ \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of $A_N$ and its $t$-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this $\sqrt{s}$, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at $\sqrt{s_{NN}} = 200$ GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, $\eta/s$, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of $\eta/s$ that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.