Helix 02

N. Weinrich, M. Boudaud, L. Derome, Y. Génolini, J. Lavalle, D. Maurin, P. Salati, P. Serpico, G. Weymann-Despres

Context. The vertical diffusive halo size of the Galaxy, L, is a key parameter for dark matter indirect searches. It can be better determined thanks to recent AMS-02 data. Aims. We set constraints on L from Be/B and 10Be/Be data, and we performed a consistency check with positron data. We detail the dependence of Be/B and 10Be/Be on L and forecast on which energy range better data would be helpful for future L improvements. Methods. We used USINE V3.5 for the propagation of nuclei, and e+ were calculated with the pinching method. Results. The current AMS-02 Be/B (∼3% precision) and ACE-CRIS 10Be/Be (∼10% precision) data bring similar and consistent constraints on L. The AMS-02 Be/B data alone constrain L = 5−2+3 kpc at a 68% confidence level (spanning different benchmark transport configurations), a range for which most models do not overproduce positrons. Future experiments need to deliver percent-level accuracy on 10Be/9Be anywhere below 10 GV to further constrain L. Conclusions. Forthcoming AMS-02, HELIX, and PAMELA 10Be/9Be results will further test and possibly tighten the limits derived here. Elemental ratios involving radioactive species with different lifetimes (e.g. Al/Mg and Cl/Ar) are also awaited to provide complementary and robuster constraints.

Shan Gao, Caihua Li, Xiaohui Chen, Sida Li, Nansong Liang, Hengtao Wang, Yaguang Zhan, Fansuo Zeng

The basic helix-loop-helix (bHLH) transcription factors (TFs) are involved in plant morphogenesis and various abiotic and biotic stress responses. However, it requires further exploration of drought-responsive bHLH family members and their detailed regulatory mechanisms in Populus. Two bHLH TF genes, PxbHLH01/02, were identified in Populus simonii × P. nigra and cloned. The aim of this study was to examine the role of bHLH TFs in drought tolerance in P. simonii × P. nigra. The results showed that the amino acid sequences of the two genes were homologous to Arabidopsis thaliana UPBEAT1 (AtUPB1) and overexpression of PxbHLH01/02 restored normal root length in the AtUPB1 insertional mutant (upb1-1). The PxbHLH01/02 gene promoter activity analysis suggested that they were involved in stress responses and hormone signaling. Furthermore, Arabidopsis transgenic lines overexpressing PxbHLH01/02 exhibited higher stress tolerance compared with the wild-type. P. simonii × P. nigra overexpressing PxbHLH02 increased drought tolerance and exhibited higher superoxide dismutase and peroxidase activities, lower H2O2 and malondialdehyde (MDA) content, and lower relative conductivity. The results of transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) suggested that the response of PxbHLH02 to drought stress was related to ABA signal transduction. Overall, the findings of this study suggest that PxbHLH02 from P. simonii × P. nigra functions as a positive regulator of drought stress responses by regulating stomatal aperture and promoting ABA signal transduction.

Philippa M. Saunders, B. MacLachlan, Jacqueline M. L. Widjaja, S. C. Wong, Clare V. L. Oates, J. Rossjohn, J. Vivian, A. Brooks

Key Points NK cells are differentially inhibited by HLA-ABw4 interactions with KIR3DL1. Residues within the HLA class I α2 helix contribute to defining KIR3DL1 ligands. KIR3DL1 binds HLA-ABw4 ligands via the same contacts as HLA-BBw4 ligands. Visual Abstract HLA class I molecules that represent ligands for the inhibitory killer cell Ig-like receptor (KIR) 3DL1 found on NK cells are categorically defined as those HLA-A and HLA-B allotypes containing the Bw4 motif, yet KIR3DL1 demonstrates hierarchical recognition of these HLA-Bw4 ligands. To better understand the molecular basis underpinning differential KIR3DL1 recognition, the HLA-ABw4 family of allotypes were investigated. Transfected human 721.221 cells expressing HLA-A*32:01 strongly inhibited primary human KIR3DL1+ NK cells, whereas HLA-A*24:02 and HLA-A*23:01 displayed intermediate potency and HLA-A*25:01 failed to inhibit activation of KIR3DL1+ NK cells. Structural studies demonstrated that recognition of HLA-A*24:02 by KIR3DL1 used identical contacts as the potent HLA-B*57:01 ligand. Namely, the D1–D2 domains of KIR3DL1 were placed over the α1 helix and α2 helix of the HLA-A*24:02 binding cleft, respectively, whereas the D0 domain contacted the side of the HLA-A*24:02 molecule. Nevertheless, functional analyses showed KIR3DL1 recognition of HLA-A*24:02 was more sensitive to substitutions within the α2 helix of HLA-A*24:02, including residues Ile142 and Lys144. Furthermore, the presence of Thr149 in the α2 helix of HLA-A*25:01 abrogated KIR3DL1+ NK inhibition. Together, these data demonstrate a role for the HLA class I α2 helix in determining the hierarchy of KIR3DL1 ligands. Thus, recognition of HLA class I is dependent on a complex interplay between the peptide repertoire, polymorphisms within and proximal to the Bw4 motif, and the α2 helix. Collectively, the data furthers our understanding of KIR3DL1 ligands and will inform genetic association and immunogenetics studies examining the role of KIR3DL1 in disease settings.

Sushma Anand, D. Littler, J. Mobbs, Asolina Braun, D. Baker, Luke Tennant, A. Purcell, J. Vivian, J. Rossjohn

Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vβ13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR–HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C.

Christopher F. Liu, K. Prasad, A. Moretta, P. Vijayaraman, F. Zanon, Camden Harrell, Crystal Miller, M. Gleva, J. de Pooter, Larry A. Chinitz