tetano
Editor, Senior Moderator
Immune Netw
. 2025 Feb 7;25(2):e4.
doi: 10.4110/in.2025.25.e4. eCollection 2025 Apr. Patients With Mild COVID-19 Exhibit Low Functional Avidity of SARS-CoV-2 Membrane Protein-Reactive CD4[SUP]+[/SUP] T Cells
A-Reum Kim[SUP] 1 2 [/SUP], June-Young Koh[SUP] 2 [/SUP], Min-Seok Rha[SUP] 2 [/SUP], Jae Hyung Jung[SUP] 2 [/SUP], Jae-Hoon Ko[SUP] 3 [/SUP], Hee Kyoung Choi[SUP] 4 [/SUP], Ji Hoon Jeon[SUP] 4 [/SUP], Hyeri Seok[SUP] 4 [/SUP], Dae Won Park[SUP] 4 [/SUP], Kyong Ran Peck[SUP] 3 [/SUP], Jun Yong Choi[SUP] 5 [/SUP], Su-Hyung Park[SUP] 2 6 [/SUP], Won Suk Choi[SUP] 4 [/SUP], Hye Won Jeong[SUP] 7 [/SUP], Eui-Cheol Shin[SUP] 1 2 [/SUP]
Affiliations
Herein, we found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-unexposed individuals exhibited an increased frequency of CD4[SUP]+[/SUP] T cells against SARS-CoV-2 membrane (M) protein, suggesting that SARS-CoV-2 M-reactive cells may be primed by previous infection with common cold coronaviruses (CCCoVs). We confirmed that CCCoV M-reactive CD4[SUP]+[/SUP] T cells cross-recognize SARS-CoV-2 M in unexposed individuals. Among coronavirus disease 2019 (COVID-19) convalescents and unexposed individuals, SARS-CoV-2 M-reactive CD4[SUP]+[/SUP] T cells exhibited significantly lower functional avidity than CD4[SUP]+[/SUP] T cells reactive to other viruses. Importantly, convalescents from mild COVID-19 had SARS-CoV-2 M-reactive CD4[SUP]+[/SUP] T cells with significantly lower functional avidity than convalescents from severe COVID-19. The current data suggest that pre-existing CCCoV M-specific memory CD4[SUP]+[/SUP] T cells may contribute to controlling SARS-CoV-2 infection by cross-reactivity, leading to mild disease but leaving memory cells with low functional avidity to SARS-CoV-2 M due to incomplete homology. These data provide indirect evidence that pre-existing cross-reactive CD4[SUP]+[/SUP] T cells contribute to protection from severe COVID-19.
Keywords: CD4-positive-T-lymphocytes; COVID-19; Cross-reactivity; Functional avidity; SARS-CoV-2
. 2025 Feb 7;25(2):e4.
doi: 10.4110/in.2025.25.e4. eCollection 2025 Apr. Patients With Mild COVID-19 Exhibit Low Functional Avidity of SARS-CoV-2 Membrane Protein-Reactive CD4[SUP]+[/SUP] T Cells
A-Reum Kim[SUP] 1 2 [/SUP], June-Young Koh[SUP] 2 [/SUP], Min-Seok Rha[SUP] 2 [/SUP], Jae Hyung Jung[SUP] 2 [/SUP], Jae-Hoon Ko[SUP] 3 [/SUP], Hee Kyoung Choi[SUP] 4 [/SUP], Ji Hoon Jeon[SUP] 4 [/SUP], Hyeri Seok[SUP] 4 [/SUP], Dae Won Park[SUP] 4 [/SUP], Kyong Ran Peck[SUP] 3 [/SUP], Jun Yong Choi[SUP] 5 [/SUP], Su-Hyung Park[SUP] 2 6 [/SUP], Won Suk Choi[SUP] 4 [/SUP], Hye Won Jeong[SUP] 7 [/SUP], Eui-Cheol Shin[SUP] 1 2 [/SUP]
Affiliations
- PMID: 40342838
- PMCID: PMC12056292
- DOI: 10.4110/in.2025.25.e4
Herein, we found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-unexposed individuals exhibited an increased frequency of CD4[SUP]+[/SUP] T cells against SARS-CoV-2 membrane (M) protein, suggesting that SARS-CoV-2 M-reactive cells may be primed by previous infection with common cold coronaviruses (CCCoVs). We confirmed that CCCoV M-reactive CD4[SUP]+[/SUP] T cells cross-recognize SARS-CoV-2 M in unexposed individuals. Among coronavirus disease 2019 (COVID-19) convalescents and unexposed individuals, SARS-CoV-2 M-reactive CD4[SUP]+[/SUP] T cells exhibited significantly lower functional avidity than CD4[SUP]+[/SUP] T cells reactive to other viruses. Importantly, convalescents from mild COVID-19 had SARS-CoV-2 M-reactive CD4[SUP]+[/SUP] T cells with significantly lower functional avidity than convalescents from severe COVID-19. The current data suggest that pre-existing CCCoV M-specific memory CD4[SUP]+[/SUP] T cells may contribute to controlling SARS-CoV-2 infection by cross-reactivity, leading to mild disease but leaving memory cells with low functional avidity to SARS-CoV-2 M due to incomplete homology. These data provide indirect evidence that pre-existing cross-reactive CD4[SUP]+[/SUP] T cells contribute to protection from severe COVID-19.
Keywords: CD4-positive-T-lymphocytes; COVID-19; Cross-reactivity; Functional avidity; SARS-CoV-2