An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease

被引：121

作者：

Peng, Yanchun ^{[1
,2
]}

Felce, Suet Ling ^{[2
,3
,4
]}

Dong, Danning ^{[1
,2
,5
]}

Penkava, Frank ^{[6
]}

Mentzer, Alexander J. ^{[3
,4
]}

Yao, Xuan ^{[2
,4
]}

Liu, Guihai ^{[2
,4
,7
]}

Yin, Zixi ^{[1
,2
,4
]}

Chen, Ji-Li ^{[1
,2
]}

Lu, Yongxu ^{[8
]}

Wellington, Dannielle ^{[1
,2
]}

Wing, Peter A. C. ^{[2
,4
]}

Dominey-Foy, Delaney C. C. ^{[2
,4
]}

Jin, Chen ^{[2
,4
]}

Wang, Wenbo ^{[2
,4
]}

Abd Hamid, Megat ^{[2
,4
]}

Fernandes, Ricardo A. ^{[2
,4
]}

Wang, Beibei ^{[2
,4
]}

Fries, Anastasia ^{[3
,4
]}

Zhuang, Xiaodong ^{[4
]}

Ashley, Neil ^{[9
]}

Rostron, Timothy ^{[10
]}

Waugh, Craig ^{[11
]}

Sopp, Paul ^{[11
]}

Hublitz, Philip ^{[12
]}

Beveridge, Ryan ^{[13
]}

Tan, Tiong Kit ^{[1
]}

Dold, Christina ^{[14
,15
]}

Kwok, Andrew J. ^{[3
,4
]}

Rich-Griffin, Charlotte ^{[3
]}

Dejnirattisa, Wanwisa ^{[3
,4
]}

Liu, Chang ^{[2
,3
,4
]}

Kurupati, Prathiba ^{[1
]}

Nassiri, Isar ^{[1
,3
,5
,17
]}

Watson, Robert A. ^{[16
,17
]}

Tong, Orion ^{[16
,17
]}

Taylor, Chelsea A. ^{[16
,17
]}

Sharma, Piyush Kumar ^{[16
,17
]}

Sun, Bo ^{[3
]}

Curion, Fabiola ^{[3
,18
]}

Revale, Santiago ^{[3
]}

Garner, Lucy C. ^{[17
,19
]}

Jansen, Kathrin ^{[20
]}

Ferreira, Ricardo C. ^{[3
]}

Attar, Moustafa ^{[20
]}

Fry, Jeremy W. ^{[21
]}

Russell, Rebecca A. ^{[22
]}

Stauss, Hans J. ^{[23
]}

James, William ^{[24
]}

Townsend, Alain ^{[1
,2
]}

机构：

[1] Univ Oxford, Radcliffe Dept Med, MRC Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England

[2] Univ Oxford, Chinese Acad Med Sci Oxford Inst, Oxford, England

[3] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[4] Univ Oxford, Nuffield Dept Med, Oxford, England

[5] Xinjiang Med Univ, Xinjiang Tumor Hosp, CAMS Key Lab Tumor Immunol & Radiat Therapy, Urumqi, Peoples R China

[6] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England

[7] Capital Med Univ, Beijing Youan Hosp, Beijing, Peoples R China

[8] Univ Cambridge, Dept Pathol, Cambridge, England

[9] Univ Oxford, MRC Weatherall Inst Mol Med, Single Cell Facil, Oxford, England

[10] Univ Oxford, MRC Weatherall Inst Mol Med, Sequencing Facil, Oxford, England

[11] Univ Oxford, MRC Weatherall Inst Mol Med, Flow Cytometry Facil, Oxford, England

[12] Univ Oxford, MRC Weatherall Inst Mol Med, Genome Engn Facil, Oxford, England

[13] Univ Oxford, MRC Weatherall Inst Mol Med, Virus Screening Facil, Oxford, England

[14] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Dept Paediat, Oxford Vaccine Grp, Oxford, England

[15] Univ Oxford, Ctr Clin Vaccinol & Trop Med, NIHR Oxford Biomed Res Ctr, Oxford, England

[16] Univ Oxford, Dept Oncol, Oxford, England

[17] Univ Oxford, MRC Weatherall Inst Mol Med, Oxford, England

[18] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Computat Biol, Neuherberg, Germany

[19] Univ Oxford, Nuffield Dept Med, Translat Gastroenterol Unit, Oxford, England

[20] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England

[21] Prolmmune Ltd, Oxford, England

[22] Univ Oxford, Sir William Dunn Sch Pathol, Oxford, England

[23] UCL, Inst Immun & Transplantat, London, England

[24] Univ Oxford, Sir William Dunn Sch Pathol, James & Lillian Martin Ctr, Oxford, England

[25] Univ Oxford, Peter Medawar Bldg Pathogen Res, Oxford, England

[26] Mahidol Univ, Fac Med, Siriaj Hosp, Dengue Hemorrhag Fever Res Unit,Off Res & Dev, Bangkok, Thailand

[27] UCL, Div Infect & Immun, London, England

来源：

NATURE IMMUNOLOGY | 2022年 / 23卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

RNA-SEQ; SARS-COV-2; RECOMBINANT;

D O I：

10.1038/s41590-021-01084-z

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

NP105-113-B*07:02-specific CD8(+) T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design. Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP105-113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP105-113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.

引用

页码：50 / +

页数：26

共 48 条

[1] Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses [J].

Abd Hamid, Megat ;

Colin-York, Huw ;

Khalid-Alham, Nasullah ;

Browne, Molly ;

Cerundolo, Lucia ;

Chen, Ji-Li ;

Yao, Xuan ;

Rosendo-Machado, Samara ;

Waugh, Craig ;

Maldonado-Perez, David ;

Bowes, Emma ;

Verrill, Clare ;

Cerundolo, Vincenzo ;

Conlon, Christopher P. ;

Fritzsche, Marco ;

Peng, Yanchun ;

Dong, Tao .

CANCER IMMUNOLOGY RESEARCH, 2020, 8 (02) :203-216

[2] Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8+ Tumor-Infiltrating T Lymphocyte Responses [J].

Abd Hamid, Megat ;

Wang, Ruo-Zheng ;

Yao, Xuan ;

Fan, Peiwen ;

Li, Xi ;

Chang, Xue-Mei ;

Feng, Yaning ;

Jones, Stephanie ;

Maldonado-Perez, David ;

Waugh, Craig ;

Verrill, Clare ;

Simmons, Alison ;

Cerundolo, Vincenzo ;

McMichael, Andrew ;

Conlon, Christopher ;

Wang, Xiyan ;

Peng, Yanchun ;

Dong, Tao .

CANCER IMMUNOLOGY RESEARCH, 2019, 7 (08) :1293-1306

[3]

Ahern D. J., BLOOD ATLAS COVID 19, DOI 10.1101/2021.05.11.21256877(2021

[4] Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection [J].

Akthar, Samia ;

Patel, Dhiren F. ;

Beale, Rebecca C. ;

Peiro, Teresa ;

Xu, Xin ;

Gaggar, Amit ;

Jackson, Patricia L. ;

Blalock, J. Edwin ;

Lloyd, Clare M. ;

Snelgrove, Robert J. .

NATURE COMMUNICATIONS, 2015, 6

[5] Orchestrating single-cell analysis with Bioconductor [J].

Amezquita, Robert A. ;

Lun, Aaron T. L. ;

Becht, Etienne ;

Carey, Vince J. ;

Carpp, Lindsay N. ;

Geistlinger, Ludwig ;

Marini, Federico ;

Rue-Albrecht, Kevin ;

Risso, Davide ;

Soneson, Charlotte ;

Waldron, Levi ;

Pages, Herve ;

Smith, Mike L. ;

Huber, Wolfgang ;

Morgan, Martin ;

Gottardo, Raphael ;

Hicks, Stephanie C. .

NATURE METHODS, 2020, 17 (02) :137-145

[6] Antigen receptor repertoire profiling from RNA-seq data [J].

Bolotin, Dmitriy A. ;

Poslavsky, Stanislav ;

Davydov, Alexey N. ;

Frenkel, Felix E. ;

Fanchi, Lorenzo ;

Zolotareva, Olga I. ;

Hemmers, Saskia ;

Putintseva, Ekaterina V. ;

Obraztsova, Anna S. ;

Shugay, Mikhail ;

Ataullakhanov, Ravshan I. ;

Rudensky, Alexander Y. ;

Schumacher, Ton N. ;

Chudakov, Dmitriy M. .

NATURE BIOTECHNOLOGY, 2017, 35 (10) :908-+

[7] MiXCR: software for comprehensive adaptive immunity profiling [J].

Bolotin, Dmitriy A. ;

Poslavsky, Stanislav ;

Mitrophanov, Igor ;

Shugay, Mikhail ;

Mamedov, Ilgar Z. ;

Putintseva, Ekaterina V. ;

Chudakov, Dmitriy M. .

NATURE METHODS, 2015, 12 (05) :380-381

[8]

Brunson, 2020, J OPEN SOURCE SOFTWA, DOI 10.21105/joss.02017

[9] VACCINIA VIRUS EXPRESSION VECTOR - COEXPRESSION OF BETA-GALACTOSIDASE PROVIDES VISUAL SCREENING OF RECOMBINANT VIRUS PLAQUES [J].

CHAKRABARTI, S ;

BRECHLING, K ;

MOSS, B .

MOLECULAR AND CELLULAR BIOLOGY, 1985, 5 (12) :3403-3409

[10]

Danileviciute E., 2019, PARK7 DJ 1 PROMOTES, DOI 10.1101/2019.12.20.884809v1

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