TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4(+) T Cell Response

Bhattacharyya, Nayan D.1,2; Counoupas, Claudio2,3; Daniel, Lina1,2; Zhang, Guoliang1,2,4; Cook, Stuart J.5; Cootes, Taylor A.1,2; Stifter, Sebastian A.1,2; Bowen, David G.6,7; Triccas, James A.2,3,8; Bertolino, Patrick6,7; Britton, Warwick J.2; Feng, Carl G.1,2,8

2021-06-15

10.4049/jimmunol.2001271

JOURNAL OF IMMUNOLOGY   影响因子和分区

0022-1767

1550-6606

The quality of T cell responses depends on the lymphocytes' ability to undergo clonal expansion, acquire effector functions, and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4(+) T cells with different peptide:MHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition or the functional output of individual effectors following mycobacterial infection in mice. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation, and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR binding affinity in Th1 differentiation and suggest that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens.

SCI

英语

其他

National Health and Medical Research Council, Department of Health Australia[APP1146677]

Immunology

Immunology

WOS:000664819300012

AMER ASSOC IMMUNOLOGISTS

IMMUNOLOGY

Web of Science

1.Univ Sydney, Fac Med & Hlth, Immunol & Host Def Grp, Dept Infect Dis & Immunol,Sch Med Sci, Sydney, NSW, Australia
2.Royal Prince Alfred Hosp, Centenary Inst, TB Res Program, Camperdown, NSW, Australia
3.Univ Sydney, Fac Med & Hlth, Microbial Pathogenesis & Immun Grp, Dept Infect Dis & Immunol,Sch Med Sci, Sydney, NSW, Australia
4.Southern Univ Sci & Technol, Natl Clin Res Ctr Infect Dis, Guangdong Key Lab Emerging Infect Dis, Shenzhen Peoples Hosp 3, Shenzhen, Peoples R China
5.Royal Prince Alfred Hosp, Centenary Inst, Immune Imaging Program, Camperdown, NSW, Australia
6.Royal Prince Alfred Hosp, Centenary Inst, Liver Immunol Program, Camperdown, NSW, Australia
7.Royal Prince Alfred Hosp, AW Morrow Gastroenterol & Liver Ctr, Camperdown, NSW, Australia
8.Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW, Australia

Bhattacharyya, Nayan D.,Counoupas, Claudio,Daniel, Lina,et al. TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4(+) T Cell Response[J]. JOURNAL OF IMMUNOLOGY,2021,206(12):2875-2887.

Bhattacharyya, Nayan D..,Counoupas, Claudio.,Daniel, Lina.,Zhang, Guoliang.,Cook, Stuart J..,...&Feng, Carl G..(2021).TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4(+) T Cell Response.JOURNAL OF IMMUNOLOGY,206(12),2875-2887.

Bhattacharyya, Nayan D.,et al."TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4(+) T Cell Response".JOURNAL OF IMMUNOLOGY 206.12(2021):2875-2887.