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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell 2021 ; 184 (15): 3962-3980.e17 Nephropedia Template TP
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Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs #MMPMID34171305
Weingarten-Gabbay S; Klaeger S; Sarkizova S; Pearlman LR; Chen DY; Gallagher KME; Bauer MR; Taylor HB; Dunn WA; Tarr C; Sidney J; Rachimi S; Conway HL; Katsis K; Wang Y; Leistritz-Edwards D; Durkin MR; Tomkins-Tinch CH; Finkel Y; Nachshon A; Gentili M; Rivera KD; Carulli IP; Chea VA; Chandrashekar A; Bozkus CC; Carrington M; Bhardwaj N; Barouch DH; Sette A; Maus MV; Rice CM; Clauser KR; Keskin DB; Pregibon DC; Hacohen N; Carr SA; Abelin JG; Saeed M; Sabeti PC
Cell 2021[Jul]; 184 (15): 3962-3980.e17 PMID34171305show ga
T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development.
|A549 Cells[MESH]
|Alleles[MESH]
|Amino Acid Sequence[MESH]
|Animals[MESH]
|Antigen Presentation/immunology[MESH]
|COVID-19/immunology/virology[MESH]
|Epitopes, T-Lymphocyte/*immunology[MESH]
|Female[MESH]
|HEK293 Cells[MESH]
|Histocompatibility Antigens Class I/*immunology[MESH]