VH-RELATED IDIOTOPES DETECTED BY SITE-DIRECTED MUTAGENESIS

The function of the CD4 cell surface protein as coreceptor on T helper lymphocytes and as receptor for HIV makes this glycoprotein a prime target for an immune intervention with mAb. A detailed understanding of the structural determinants on the therapeutic CD4 mAb that are involved in Ag binding or are recognized by anti-idiotypic mAb (anti-Id) may be important for designing antibodies with optimal therapeutic efficacy. Seven anti-Id raised against the CD4 mAb M-T310 were selected from a large panel with the intention to obtain CD4 mimicking structures with specificity foHr IV gp120. The selected anti-Id did not reacwt ith other CDCspecific mAb cross-blocking M-T310. Among these, mAb MT404, although having the same L chain as M-T310 and a VH region sequence differing onlya t 14 amino acid positions, was not recognized by the anti-Id. MT310 H chain complexed with the J558L L chain reacted with all anti-Id, thus demonstrating that the recognized idiotopes are located within the VH region. To identify the idiotopes of M-T310 seen by the anti-Id, variants of M-T404 containing one or more of the M-T3 1 O-derived substitutions were generated by oligonucleotide-directed mutagenesis. The reactivity pattern of the mutant proteins with the anti-Id demonstrated that the idiotopes reside within the complementarity determining region (CDR) 2 and CDR3 loops of the VH region. A major idiotope was definebdy a single amino acid in CDR2 that was recognized by three anti-Id, whereas the four other anti-Id reacted with determinants of CDR3. Although the performed amino acid substitutions did influence the Id recognition, Ag binding was not significantly affected, suggesting that none of the anti-Id can be considered as a mimicry of the CD4 A

Destabilizing the autoinhibitory conformation of Zap70 induces up-regulation of inhibitory receptors and T cell unresponsiveness.

Zap70 plays a critical role in normal T cell development and T cell function. However, little is known about how perturbation of allosteric autoinhibitory mechanisms in Zap70 impacts T cell biology. Here, we analyze mice with a hypermorphic Zap70 mutation, W131A, which destabilizes the autoinhibitory conformation of Zap70, rendering the kinase in a semiactive state. W131A mutant mice with wild-type T cell receptor (TCR) repertoires exhibited relatively normal T cell development. However, crossing the W131A mutant mice to OTII TCR transgenic mice resulted in increased negative selection of OTII+ thymocytes and in increased thymic and peripheral T regulatory cells. Strikingly, increased basal TCR signaling was associated with a marked increase in inhibitory receptor expression and with T cells that were relatively refractory to TCR stimulation. PD-1 inhibitory receptor blockade partially reversed T cell unresponsiveness. Collectively, disruption of normal Zap70 autoinhibition engaged negative feedback mechanisms by which negative selection and inhibitory receptors restrain TCR signaling to enforce both central and peripheral tolerance

All-electrical measurements of direct spin Hall effect in GaAs with Esaki diode electrodes

We report on measurements of direct spin Hall effect in a lightly n-doped GaAs channel. As spin detecting contacts we employed highly efficient ferromagnetic Fe/(Ga,Mn)As/GaAs Esaki diode structures. We investigate bias and temperature dependence of the measured spin Hall signal and evaluate the value of total spin Hall conductivity and its dependence on channel conductivity and temperature. From the results we determine skew scattering and side jump contribution to the total spin hall conductivity and compare it with the results of experiments on higher conductive n-GaAs channels[Phys. Rev. Lett. 105,156602(2010)]. As a result we conclude that both skewness and side jump contribution cannot be fully independent on the conductivity of the channel.Comment: 14 pages, 4 figure

Electric-field-induced strong enhancement of electroluminescence in multilayer molybdenum disulfide.

The layered transition metal dichalcogenides have attracted considerable interest for their unique electronic and optical properties. While the monolayer MoS2 exhibits a direct bandgap, the multilayer MoS2 is an indirect bandgap semiconductor and generally optically inactive. Here we report electric-field-induced strong electroluminescence in multilayer MoS2. We show that GaN-Al2O3-MoS2 and GaN-Al2O3-MoS2-Al2O3-graphene vertical heterojunctions can be created with excellent rectification behaviour. Electroluminescence studies demonstrate prominent direct bandgap excitonic emission in multilayer MoS2 over the entire vertical junction area. Importantly, the electroluminescence efficiency observed in multilayer MoS2 is comparable to or higher than that in monolayers. This strong electroluminescence can be attributed to electric-field-induced carrier redistribution from the lowest energy points (indirect bandgap) to higher energy points (direct bandgap) in k-space. The electric-field-induced electroluminescence is general for other layered materials including WSe2 and can open up a new pathway towards transition metal dichalcogenide-based optoelectronic devices