Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis, and is used in treatment of warts, melanoma and alopecia areata. This therapeutic setting therefore provided an opportunity to study T cell receptor (TCR) repertoire changes in response to hapten sensitization in humans. Repeated exposure to DPC induced highly dynamic transient expansions of a polyclonal diverse T cell population. The number of TCRs expanded early after sensitization varies between individuals, and predicts the magnitude of the allergic reaction. The expanded TCRs show preferential TCR V and J gene usage, and consist of clusters of TCRs with similar sequences, two characteristic features of antigen-driven responses. The expanded TCRs share subtle sequence motifs that can be captured using a Dynamic Bayesian Network. These observations suggest the response to DPC is mediated by a polyclonal population of T cells recognizing a small number of dominant antigens.
All DNA sequences have been submitted to the Short Read Archive under identifier SUB6567504 .
- Benny Chain
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: The protocol was approved by the University College London Hospital Ethics Committee 06/Q0502/92. A total of 34 patients were recruited to this study (NRES Ethics Committee East of England - Cambridgeshire and Hertfordshire [14/EE/1067]). Participants were recruited from patients who had been diagnosed with alopecia, were aged between 18 and 70, identified as suitable for DPC treatment by a consultant dermatologist, and were now attending their first visit to the Alopecia Clinic at Salford Royal Hospital for DPC therapy. This study ran alongside patients' prescribed DPC treatment (weekly doses of DPC to the scalp to induce inflammation and hair regrowth). All participants gave their informed consent to participate, and were free to withdraw from the study at any time and for any reason without affecting their treatment. Patients were excluded from the study if they were pregnant.
- Armita Nourmohammad, University of Washington, United States
© 2021, Ronel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Macrophages absorbing cells infected with viable SARS-CoV-2 particles fail to transition into an anti-inflammatory state, potentially contributing to a damaging immune reaction linked to severe forms of COVID-19.
Langerhans cells are specialized antigen-presenting cells localized within the epidermis and mucosal epithelium. Upon contact with Langerhans cells, pathogens are captured by the C-type lectin langerin and internalized into a structurally unique vesicle known as a Birbeck granule. Although the immunological role of Langerhans cells and Birbeck granules have been extensively studied, the mechanism by which the characteristic zippered membrane structure of Birbeck granules is formed remains elusive. In this study, we observed isolated Birbeck granules using cryo-electron tomography and reconstructed the 3D structure of the repeating unit of the honeycomb lattice of langerin at 6.4 Å resolution. We found that the interaction between the two langerin trimers was mediated by docking the flexible loop at residues 258–263 into the secondary carbohydrate-binding cleft. Mutations within the loop inhibited Birbeck granule formation and the internalization of HIV pseudovirus. These findings suggest a molecular mechanism for membrane zippering during Birbeck granule biogenesis and provide insight into the role of langerin in the defense against viral infection.