Citation
Habel, Jennifer R., et al. "Suboptimal SARS-CoV-2-specific CD8+ T Cell Response Associated With the Prominent HLA-A*02:01 Phenotype." Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 39, 2020, pp. 24384-24391.
Habel JR, Nguyen THO, van de Sandt CE, et al. 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. 2020;117(39):24384-24391.
Habel, J. R., Nguyen, T. H. O., van de Sandt, C. E., Juno, J. A., Chaurasia, P., Wragg, K., Koutsakos, M., Hensen, L., Jia, X., Chua, B., Zhang, W., Tan, H. X., Flanagan, K. L., Doolan, D. L., Torresi, J., Chen, W., Wakim, L. M., Cheng, A. C., Doherty, P. C., ... Kedzierska, K. (2020). Suboptimal SARS-CoV-2-specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype. Proceedings of the National Academy of Sciences of the United States of America, 117(39), 24384-24391. https://doi.org/10.1073/pnas.2015486117
Habel JR, et al. 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. 2020 09 29;117(39):24384-24391. PubMed PMID: 32913053.
TY - JOUR
T1 - Suboptimal SARS-CoV-2-specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype.
AU - Habel,Jennifer R,
AU - Nguyen,Thi H O,
AU - van de Sandt,Carolien E,
AU - Juno,Jennifer A,
AU - Chaurasia,Priyanka,
AU - Wragg,Kathleen,
AU - Koutsakos,Marios,
AU - Hensen,Luca,
AU - Jia,Xiaoxiao,
AU - Chua,Brendon,
AU - Zhang,Wuji,
AU - Tan,Hyon-Xhi,
AU - Flanagan,Katie L,
AU - Doolan,Denise L,
AU - Torresi,Joseph,
AU - Chen,Weisan,
AU - Wakim,Linda M,
AU - Cheng,Allen C,
AU - Doherty,Peter C,
AU - Petersen,Jan,
AU - Rossjohn,Jamie,
AU - Wheatley,Adam K,
AU - Kent,Stephen J,
AU - Rowntree,Louise C,
AU - Kedzierska,Katherine,
Y1 - 2020/09/10/
PY - 2020/9/12/pubmed
PY - 2020/10/21/medline
PY - 2020/9/11/entrez
KW - CD8+ T cells
KW - COVID-19
KW - HLA-A*02:01
KW - SARS-CoV-2 epitopes
SP - 24384
EP - 24391
JF - Proceedings of the National Academy of Sciences of the United States of America
JO - Proc Natl Acad Sci U S A
VL - 117
IS - 39
N2 - 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/S269-277 and A2/Orf1ab3183-3191 Using peptide-HLA tetramer enrichment, direct ex vivo assessment of A2/S269 +CD8+ and A2/Orf1ab3183 +CD8+ populations indicated that A2/S269 +CD8+ T cells were detected at comparable frequencies (∼1.3 × 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 (∼2.5 × 10-6), but low when compared to frequencies for influenza-specific (A2/M158) and Epstein-Barr virus (EBV)-specific (A2/BMLF1280) (∼1.38 × 10-4) populations. Phenotyping A2/S269 +CD8+ T cells from COVID-19 convalescents ex vivo showed that A2/S269 +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 naïve, stem cell memory and central memory A2/S269 +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.
SN - 1091-6490
UR - https://www.unboundmedicine.com/medline/citation/32913053/Suboptimal_SARS_CoV_2_specific_CD8+_T_cell_response_associated_with_the_prominent_HLA_A_02:01_phenotype_
L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=32913053
DB - PRIME
DP - Unbound Medicine
ER -