Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination

Viral escape from CD8+ cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8+ T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape

Using ‘‘domino’’ model to study the secular variation of the geomagnetic dipolar moment

Aiming to understand the physical processes underneath the reversals events of geomagnetic field, different numerical models have been conceived. We considered here the so named ‘‘domino’’ model, an Ising–Heisenberg model of interacting magnetic macrospins aligned along a ring. This model was proposed by Mazaud and Laj (1989) and then applied by Mori et al. (2013) to study geomagnetic field reversals. The long series of the axial magnetic moment (dipolar moment or ‘‘magnetization’’) generated by the ‘‘domino’’ model are empirically studied by varying all model parameters. We present here some results which are slightly different from those given by Mori et al. (2013), and will provide our explanation on the presence of these differences. We also define the set of parameters that supply the longest mean time between reversals. Using this set of parameters, a large number of time series of axial magnetic moment are also generated. After de-noising the fluctuation of these time series and averaging them, we compared the resulting averaged series with the series of axial dipolar magnetic moment values supplied by CALS7k.2, and CALS10k.1b models, finding similar behavior for the all time series. In a similar way, we also compared the averaged 14,000 years long series of dipolar moment with the dipolar magnetic moment obtained by the model SHA.DIF.14k

Using ‘‘domino’’ model to study the secular variation of the geomagnetic dipolar moment

Aiming to understand the physical processes underneath the reversals events of geomagnetic field, different numerical models have been conceived. We considered here the so named ‘‘domino’’ model, an Ising–Heisenberg model of interacting magnetic macrospins aligned along a ring. This model was proposed by Mazaud and Laj (1989) and then applied by Mori et al. (2013) to study geomagnetic field reversals. The long series of the axial magnetic moment (dipolar moment or ‘‘magnetization’’) generated by the ‘‘domino’’ model are empirically studied by varying all model parameters. We present here some results which are slightly different from those given by Mori et al. (2013), and will provide our explanation on the presence of these differences. We also define the set of parameters that supply the longest mean time between reversals. Using this set of parameters, a large number of time series of axial magnetic moment are also generated. After de-noising the fluctuation of these time series and averaging them, we compared the resulting averaged series with the series of axial dipolar magnetic moment values supplied by CALS7k.2, and CALS10k.1b models, finding similar behavior for the all time series. In a similar way, we also compared the averaged 14,000 years long series of dipolar moment with the dipolar magnetic moment obtained by the model SHA.DIF.14k.Published9-231A. Geomagnetismo e PaleomagnetismoJCR Journalrestricte