tetano
Editor, Senior Moderator
PLoS Pathog
. 2020 Aug 4;16(8):e1008714.
doi: 10.1371/journal.ppat.1008714. Online ahead of print.
HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells
Sneha Sant[SUP] 1 [/SUP], Sergio M Qui?ones-Parra[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Emma J Grant[SUP] 1 [/SUP], Thomas Loudovaris[SUP] 2 [/SUP], Stuart I Mannering[SUP] 2 [/SUP], Jane Crowe[SUP] 3 [/SUP], Carolien E van de Sandt[SUP] 1 4 [/SUP], Guus F Rimmelzwaan[SUP] 5 [/SUP], Jamie Rossjohn[SUP] 6 7 8 [/SUP], Stephanie Gras[SUP] 6 7 [/SUP], Liyen Loh[SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Katherine Kedzierska[SUP] 1 [/SUP]
Affiliations
Abstract
Seasonal influenza virus infections cause 290,000-650,000 deaths annually and severe morbidity in 3-5 million people. CD8+ T-cell responses towards virus-derived peptide/human leukocyte antigen (HLA) complexes provide the broadest cross-reactive immunity against human influenza viruses. Several universally-conserved CD8+ T-cell specificities that elicit prominent responses against human influenza A viruses (IAVs) have been identified. These include HLA-A*02:01-M158-66 (A2/M158), HLA-A*03:01-NP265-273, HLA-B*08:01-NP225-233, HLA-B*18:01-NP219-226, HLA-B*27:05-NP383-391 and HLA-B*57:01-NP199-207. The immunodominance hierarchies across these universal CD8+ T-cell epitopes were however unknown. Here, we probed immunodominance status of influenza-specific universal CD8+ T-cells in HLA-I heterozygote individuals expressing two or more universal HLAs for IAV. We found that while CD8+ T-cell responses directed towards A2/M158 were generally immunodominant, A2/M158+CD8+ T-cells were markedly diminished (subdominant) in HLA-A*02:01/B*27:05-expressing donors following ex vivo and in vitro analyses. A2/M158+CD8+ T-cells in non-HLA-B*27:05 individuals were immunodominant, contained optimal public TRBV19/TRAV27 TCRαβ clonotypes and displayed highly polyfunctional and proliferative capacity, while A2/M158+CD8+ T cells in HLA-B*27:05-expressing donors were subdominant, with largely distinct TCRαβ clonotypes and consequently markedly reduced avidity, proliferative and polyfunctional efficacy. Our data illustrate altered immunodominance patterns and immunodomination within human influenza-specific CD8+ T-cells. Accordingly, our work highlights the importance of understanding immunodominance hierarchies within individual donors across a spectrum of prominent virus-specific CD8+ T-cell specificities prior to designing T cell-directed vaccines and immunotherapies, for influenza and other infectious diseases.
. 2020 Aug 4;16(8):e1008714.
doi: 10.1371/journal.ppat.1008714. Online ahead of print.
HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells
Sneha Sant[SUP] 1 [/SUP], Sergio M Qui?ones-Parra[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Emma J Grant[SUP] 1 [/SUP], Thomas Loudovaris[SUP] 2 [/SUP], Stuart I Mannering[SUP] 2 [/SUP], Jane Crowe[SUP] 3 [/SUP], Carolien E van de Sandt[SUP] 1 4 [/SUP], Guus F Rimmelzwaan[SUP] 5 [/SUP], Jamie Rossjohn[SUP] 6 7 8 [/SUP], Stephanie Gras[SUP] 6 7 [/SUP], Liyen Loh[SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Katherine Kedzierska[SUP] 1 [/SUP]
Affiliations
- PMID: 32750095
- DOI: 10.1371/journal.ppat.1008714
Abstract
Seasonal influenza virus infections cause 290,000-650,000 deaths annually and severe morbidity in 3-5 million people. CD8+ T-cell responses towards virus-derived peptide/human leukocyte antigen (HLA) complexes provide the broadest cross-reactive immunity against human influenza viruses. Several universally-conserved CD8+ T-cell specificities that elicit prominent responses against human influenza A viruses (IAVs) have been identified. These include HLA-A*02:01-M158-66 (A2/M158), HLA-A*03:01-NP265-273, HLA-B*08:01-NP225-233, HLA-B*18:01-NP219-226, HLA-B*27:05-NP383-391 and HLA-B*57:01-NP199-207. The immunodominance hierarchies across these universal CD8+ T-cell epitopes were however unknown. Here, we probed immunodominance status of influenza-specific universal CD8+ T-cells in HLA-I heterozygote individuals expressing two or more universal HLAs for IAV. We found that while CD8+ T-cell responses directed towards A2/M158 were generally immunodominant, A2/M158+CD8+ T-cells were markedly diminished (subdominant) in HLA-A*02:01/B*27:05-expressing donors following ex vivo and in vitro analyses. A2/M158+CD8+ T-cells in non-HLA-B*27:05 individuals were immunodominant, contained optimal public TRBV19/TRAV27 TCRαβ clonotypes and displayed highly polyfunctional and proliferative capacity, while A2/M158+CD8+ T cells in HLA-B*27:05-expressing donors were subdominant, with largely distinct TCRαβ clonotypes and consequently markedly reduced avidity, proliferative and polyfunctional efficacy. Our data illustrate altered immunodominance patterns and immunodomination within human influenza-specific CD8+ T-cells. Accordingly, our work highlights the importance of understanding immunodominance hierarchies within individual donors across a spectrum of prominent virus-specific CD8+ T-cell specificities prior to designing T cell-directed vaccines and immunotherapies, for influenza and other infectious diseases.