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10.1073/pnas.2015486117 http://scihub22266oqcxt.onion/10.1073/pnas.2015486117 32913053!7533701!32913053     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2020 ; 117 (39): 24384-24391 Nephropedia Template TP {{tp|p=32913053|t=2020. Suboptimal SARS-CoV-2-specific CD8(+) T cell response associated with the prominent HLA-A*02:01 phenotype |pdf=|usr=}}{{32913053}} gab.com Text Suboptimal SARS-CoV-2-specific CD8(+) T cell response associated with the prominent HLA-A*02:01 phenotype JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=32913053 #FOAvip An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8(+) T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2-specific CD8(+) and CD4(+) T cells in vitro, with CD4(+) T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8(+) T cell epitopes, A2/S(269-277) and A2/Orf1ab(3183-3191) Using peptide-HLA tetramer enrichment, direct ex vivo assessment of A2/S(269)(+)CD8(+) and A2/Orf1ab(3183)(+)CD8(+) populations indicated that A2/S(269)(+)CD8(+) T cells were detected at comparable frequencies ( approximately 1.3 x 10(-5)) in acute and convalescent HLA-A*02:01(+) patients. These frequencies were higher than those found in uninfected HLA-A*02:01(+) donors ( approximately 2.5 x 10(-6)), but low when compared to frequencies for influenza-specific (A2/M1(58)) and Epstein-Barr virus (EBV)-specific (A2/BMLF(1280)) ( approximately 1.38 x 10(-4)) populations. Phenotyping A2/S(269)(+)CD8(+) T cells from COVID-19 convalescents ex vivo showed that A2/S(269)(+)CD8(+) T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8(+) T cells expressed granzymes and/or perforin. Furthermore, the bias toward naive, stem cell memory and central memory A2/S(269)(+)CD8(+) T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8(+) T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8(+) T cell immunity in COVID-19. Twit Text FOAVip Suboptimal SARS-CoV-2-specific CD8(+) T cell response associated with the prominent HLA-A*02:01 phenotype ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=32913053 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32913053 #FOAvip English Wikipedia <ref>{{Cite pmid|32913053}}</ref> Suboptimal SARS-CoV-2-specific CD8(+) T cell response associated with the prominent HLA-A*02:01 phenotype #MMPMID32913053 Habel JR; Nguyen THO; van de Sandt CE; Juno JA; Chaurasia P; Wragg K; Koutsakos M; Hensen L; Jia X; Chua B; Zhang W; Tan HX; Flanagan KL; Doolan DL; Torresi J; Chen W; Wakim LM; Cheng AC; Doherty PC; Petersen J; Rossjohn J; Wheatley AK; Kent SJ; Rowntree LC; Kedzierska K Proc Natl Acad Sci U S A 2020[Sep]; 117 (39): 24384-24391 PMID32913053show ga An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8(+) T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2-specific CD8(+) and CD4(+) T cells in vitro, with CD4(+) T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8(+) T cell epitopes, A2/S(269-277) and A2/Orf1ab(3183-3191) Using peptide-HLA tetramer enrichment, direct ex vivo assessment of A2/S(269)(+)CD8(+) and A2/Orf1ab(3183)(+)CD8(+) populations indicated that A2/S(269)(+)CD8(+) T cells were detected at comparable frequencies ( approximately 1.3 x 10(-5)) in acute and convalescent HLA-A*02:01(+) patients. These frequencies were higher than those found in uninfected HLA-A*02:01(+) donors ( approximately 2.5 x 10(-6)), but low when compared to frequencies for influenza-specific (A2/M1(58)) and Epstein-Barr virus (EBV)-specific (A2/BMLF(1280)) ( approximately 1.38 x 10(-4)) populations. Phenotyping A2/S(269)(+)CD8(+) T cells from COVID-19 convalescents ex vivo showed that A2/S(269)(+)CD8(+) T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8(+) T cells expressed granzymes and/or perforin. Furthermore, the bias toward naive, stem cell memory and central memory A2/S(269)(+)CD8(+) T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8(+) T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8(+) T cell immunity in COVID-19. |Betacoronavirus/*immunology[MESH] |CD4-Positive T-Lymphocytes/immunology[MESH] |CD8-Positive T-Lymphocytes/*immunology[MESH] |COVID-19[MESH] |Coronavirus Infections/*immunology[MESH] |Epitopes, T-Lymphocyte[MESH] |Female[MESH] |HLA-A2 Antigen/*immunology[MESH] |Humans[MESH] |Immunologic Memory[MESH] |Immunophenotyping[MESH] |Leukocytes, Mononuclear/immunology[MESH] |Lymphocyte Activation[MESH] |Male[MESH] |Middle Aged[MESH] |Pandemics[MESH] |Peptide Fragments/chemistry/immunology[MESH] |Pneumonia, Viral/*immunology[MESH] |Polyproteins[MESH] |SARS-CoV-2[MESH] |Spike Glycoprotein, Coronavirus/chemistry/immunology[MESH]Suboptimal SARS-CoV-2-specific CD8(+) T cell response associated with (epmc).pdf DeepDyve Pubget Overpricing