Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

被引：4

作者：

Milighetti, Martina ^{[1
]}

Peng, Yanchu ^{[2
,3
]}

Tan, Cedric ^{[5
]}

Mark, Michal ^{[6
]}

Nageswaran, Gayathri ^{[1
]}

Byrne, Suzanne ^{[1
]}

Ronel, Tahel ^{[1
]}

Peacock, Tom ^{[1
]}

Mayer, Andreas ^{[1
]}

Chandran, Aneesh ^{[1
]}

Rosenheim, Joshua ^{[1
]}

Whelan, Matthew ^{[1
]}

Yao, Xuan ^{[3
]}

Liu, Guihai ^{[3
]}

Felce, Suet Ling ^{[3
]}

Dong, Tao ^{[2
,3
]}

Mentzer, Alexander J. ^{[4
]}

Knight, Julian C. ^{[3
,4
]}

Balloux, Francois ^{[5
]}

Greenstein, Erez ^{[6
]}

Reich-Zeliger, Shlomit ^{[6
]}

Pade, Corinna ^{[7
]}

Gibbons, Joseph M. ^{[7
]}

Semper, Amanda ^{[8
]}

Brooks, Tim ^{[8
]}

Otter, Ashley ^{[8
]}

Altmann, Daniel M. ^{[9
]}

Boyton, Rosemary J. ^{[10
,11
]}

Maini, Mala K. ^{[1
]}

McKnight, Aine ^{[7
]}

Manisty, Charlotte ^{[12
]}

Treibel, Thomas A. ^{[12
]}

Moon, James C. ^{[12
]}

COVIDsortium Investigators, COVIDsortium Investigators

Noursadeghi, Mahdad ^{[1
]}

Chain, Benny ^{[1
]}

机构：

[1] UCL, Div Infect & Immun, London WC1E 6BT, England

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

[3] Univ Oxford, Oxford Inst COI, Chinese Acad Med Sci CAMS, Oxford, England

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

[5] UCL, UCL Genet Inst, London WC1E 6BT, England

[6] Weizmann Inst Sci, Dept Syst Immunol, IL-7610001 Rehovot, Israel

[7] Queen Mary Univ London, Blizard Inst, Barts & London Sch Med & Dent, London E1 4NS, England

[8] UK Hlth Secur Agcy, Salisbury SP4 0JG, England

[9] Imperial Coll London, Dept Immunol & Inflammat, London SW7 2BX, England

[10] Imperial Coll London, Dept Infect Dis, London W12 0NN, England

[11] Guys & St Thomas NHS Fdn Trust, Royal Brompton Hosp, Lung Div, London, England

[12] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England

来源：

ISCIENCE | 2023年 / 26卷 / 06期

基金：

“创新英国”项目; 美国国家卫生研究院; 欧盟地平线“2020”; 英国惠康基金; 英国医学研究理事会;

关键词：

LYMPHOCYTIC CHORIOMENINGITIS VIRUS; DYNAMICS; CD4(+); SEQUENCES; RESPONSES; DISEASE;

D O I：

10.1016/j.isci.2023.106937

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individ-ual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the ex-panding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lympho-cytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection.

引用

页数：21

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