St. Jude Reference #SJ-22-0003
SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, researchers at St. Jude evaluated the T cell receptor sequences and phenotype of lymph node TFH. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1∗04-restricted response to S167–180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months and can provide an easy way to access CD4 T cell memory responses in more than half of the worldwide population. Collectively, the results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.
The researchers utilize TCRalpha, instead of TCRbeta chain TCR repertoire sequencing (like the T-Detect test from Adaptive Biotechnologies), as the single alpha chain TCR motif identifies memory CD4 T cells after SARS-CoV-2 infection or importantly, vaccination with high specificity, and it recognizes an immunodominant epitope present in all DPB1*04:01/04:02 individuals. Thus, unlike other tests for T cell immunity we know exactly the limitation of this test (having appropriate HLA alleles), while others don’t account for HLA-diversity to get the result.
The T cell response to this epitope can be found by using any of the following methods:
MHC-multimer staining combined with other surface markers of T cells can also provide information about the quality of these memory T cells. This can be important to:
COVID-19; T follicular helper cell; lymph node; CD4+ T cell; mRNA vaccination; TCR repertoire; SARS-CoV-2; human immunology
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Volume 185, Issue 4, 2022, Pages 603-613.e15, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2021.12.026.
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