To better understand primary and recall T cell responses during COVID-19, it is important to examine unmanipulated SARS-CoV-2-specific T cells. Using peptide-HLA tetramers for direct ex vivo analysis, we characterized CD8 + T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8 + T cells directed towards subdominant epitopes – B7/N 257 , A2/S 269 and A24/S 1208 – CD8 + T cells specific for the immunodominant B7/N 105 epitope were detected at high frequency in pre-pandemic samples, and at increased frequency during acute COVID-19 and convalescence. SARS-CoV-2-specific CD8 + T cells in pre-pandemic samples from children, adults and elderly individuals predominantly displayed a naïve phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαβ repertoires and promiscuous αβ-TCR pairing within B7/N 105 + CD8 + T cells. Our study demonstrates high naive precursor frequency and TCRαβ diversity within immunodominant B7/N 105 -specific CD8 + T cells, and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses.

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Using reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry we investigated the ontogeny of renin, angiotensinogen and angiotensin converting enzyme (ACE) in the mesonephros at 27 and 41 days of gestation, and the metanephros at 41 and 64 days of gestation in ovine fetuses (term is 145 to 150 days). The volume and composition of fetal urine, stored as allantoic fluid were measured in 12 fetuses at 27 days, and 13 fetuses at 41 days. Renin, angiotensinogen and ACE were identified in both meso- and metanephroi at 41 days but not in the mesonephros at 27 to 30 days. Allantoic fluid volumes were 21 +/- 3 and 45 +/- 5 ml at 27 to 30 days and 41 days, respectively. This fluid was significantly different in composition to that of amniotic fluid or maternal plasma. The results suggest that the mesonephros can substantially modify its glomerular filtrate by 27 days of gestation, and can produce local angiotensin II by 41 days.