The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Transport of Snow by the Wind: A Comparison Between Observations in Adélie Land, Antarctica, and Simulations Made with the Regional Climate Model MAR

For the first time a simulation of blowing snow events was validated in detail using one-month long observations (January 2010) made in Adélie Land, Antarctica. A regional climate model featuring a coupled atmosphere/blowing snow/snowpack model is forced laterally by meteorological re-analyses. The vertical grid spacing was 2 m from 2 to 20 m above the surface and the horizontal grid spacing was 5 km. The simulation was validated by comparing the occurrence of blowing snow events and other meteorological parameters at two automatic weather stations. The Nash test allowed us to compute effi- ciencies of the simulation. The regional climate model simulated the observed wind speed with a positive efficiency (0.69). Wind speeds higher than 12 m s−1 were underestimated. Positive efficiency of the simulated wind speed was a prerequisite for validating the blowing snow model. Temperatures were simulated with a slightly negative efficiency (−0.16) due to overestimation of the amplitude of the diurnal cycle during one week, probably because the cloud cover was underestimated at that location during the period concerned. Snowfall events were correctly simulated by our model, as confirmed by field reports. Because observations suggested that our instrument (an acoustic sounder) tends to overestimate the blowing snow flux, data were not sufficiently accurate to allow the complete validation of snow drift val- ues. However, the simulation of blowing snow occurrence was in good agreement with the observations made during the first 20 days of January 2010, despite the fact that the blowing snow flux may be underestimated by the regional climate model during pure blowing snow events. We found that blowing snow occurs in Adélie Land only when the 30-min wind speed value at 2 m a.g.l. is >10 m s−1. The validation for the last 10 days of January 2010 was less satisfactory because of complications introduced by surface melting and refreezing