Large‐Scale Screening of CD4⁺ T‐Cell Epitopes From SARS‐CoV‐2 Proteins and the Universal Detection of SARS‐CoV‐2 Specific T Cells for Northeast Asian Population

ABSTRACT

The polymorphism of human leukocyte antigens in the Northeast Asian populations and the lack of broad‐spectrum T‐cell epitopes covering this cohort markedly limited the development of T cell‐directed vaccines against SARS‐CoV‐2 infection, and also hampered the universal detection of SARS‐CoV‐2 specific T cells. In this study, 93 CD4⁺ T‐cell epitopes restricted by 12 prevalent HLA‐DRB1 allotypes, which covering over 80% Chinese and Northeast Asian populations, were identified from the S, E, M, N and RdRp proteins of SARS‐CoV‐2 by in silico prediction, DC‐peptide‐PBL coculture experiment, and immunization in HLA‐A2/DR1 transgenic mice. Furthermore, by using validated 215 CD8⁺ T cell epitope peptides and 123 CD4⁺ T‐cell epitope peptides covering Northeast Asian cohort, the universal ELISpot detection systems of SARS‐CoV‐2 specific CD8⁺ T cells and CD4⁺ T cells were established, for the first time, and followed by the tests for 50 unexposed and 100 convalescent samples. The median of spot‐forming units for CD8⁺ T cells and CD4⁺ T cells were 68 and 15, respectively, in the unexposed donors, but were 137 and 52 in the convalescent donors 6 months after recovery while 128 and 47 in the convalescent donors 18 months after recovery. This work initially provided the broad‐spectrum CD4⁺ T‐cell epitope library of SARS‐CoV‐2 for the design of T cell‐directed vaccines and the universal T cell detection tool tailoring to Northeast Asian population, and confirmed the long‐term memory T cell immunity after SARS‐CoV‐2 infection.