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Although the Omicron variant of the SARS-CoV-2 virus is resistant to neutralizing antibodies, it retains susceptibility to cellular immunity. Here, we characterized vaccine-induced T cells specific for various SARS-CoV-2 variants and identified HLA-A*24:02-restricted CD8+ T cells that strongly suppressed Omicron BA.1 replication. Mutagenesis analyses revealed that a G446S mutation, located just outside the N-terminus of the cognate epitope, augmented TCR recognition of this variant. In contrast, no enhanced suppression of replication was observed against cells infected with the prototype, Omicron BA.2, and Delta variants that express G446. The enhancing effect of the G446S mutation was lost when target cells were treated with inhibitors of tripeptidyl peptidase II, a protein that mediates antigen processing. These results demonstrate that the G446S mutation in the Omicron BA.1 variant affects antigen processing/presentation and potentiates antiviral activity by vaccine-induced T cells, leading to enhanced T cell immunity towards emerging variants.
RESUMO
<p><b>OBJECTIVE</b>To explore the diagnostic feasibility of noninvasive assessment of coronary atherosclerotic plaques with MSCT in comparison with IVUS.</p><p><b>METHODS</b>Contrast-enhanced MSCT angiography (Sensation 64, Siemens Medical Solutions) was performed before percutaneous coronary intervention (PCI), and three-vessel IVUS (Boston Scientific, Natick, MA) was performed during procedure in 12 patients with stable angina pectoris. Complete investigation was digitally stored, and assessed offline with EchoPlaque (Indec Systems, Mountain View, CA). The comparison of MSCT with IVUS was performed based on segment at plaque site (American Heart Association 15-segment model).</p><p><b>RESULTS</b>A total of 88 segments in 31 vessels (left anterior descending: 12, left circumflex: 10, and right coronary artery: 9) were investigated by both IVUS and MSCT. Among 68 assessable segments (54 proximal-middle segments and 14 distal segments) by MSCT (20 segments were excluded for poor image quality: 16 for severe calcification, 2 for motion artifact, 2 for poor opacification), MSCT correctly detected 47 of the 51 segments with plaques (sensitivity: 92%), and correctly evaluated 16 of 17 segments without plaques (specificity: 94%). Concerning plaque quantification, MSCT correlated well with IVUS in grading whether the vessel obstruction was less or more than 50% (simple kappa: 0.63, 95% CI: from 0.47 to 0.78). Plaque area by MSCT also correlated with that by IVUS (r = 0.53, P < 0.01), but overestimated plaque area [(9.09 +/- 3.89) mm(2) vs. (6.80 +/- 2.81) mm(2), P < 0.01]. In addition, 30 of 43 hypoechoic compositions were detected as low-density compositions by MSCT with average CT number as 67.39 HU.</p><p><b>CONCLUSIONS</b>In segments without severe calcification, contrast-enhanced 64-slice CT angiography could detect plaques in coronary artery with high accuracy. Plaque area quantification by MSCT correlated with that of IVUS though with limited accuracy.</p>
