Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4+ T cell responses to the spike protein, including circulating follicular helper T (cTFH) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S751 tetramer to track spike-specific CD4+ T cells, we show that primary infection or vaccination induces robust S751-specific CXCR5− and cTFH cell memory responses. Secondary exposure induced recall of CD4+ T cells with a transitory CXCR3+ phenotype, and drove expansion of cTFH cells transiently expressing ICOS, CD38 and PD-1. In both contexts, cells exhibited a restricted T cell antigen receptor repertoire, including a highly public clonotype and considerable clonotypic overlap between CXCR5− and cTFH populations. Following a third vaccine dose, the rapid re-expansion of spike-specific CD4+ T cells contrasted with the comparatively delayed increase in antibody titers. Overall, we demonstrate that stable pools of cTFH and memory CD4+ T cells established by infection and/or vaccination are efficiently recalled upon antigen reexposure and may contribute to long-term protection against SARS-CoV-2.
【초록키워드】 SARS-CoV-2, coronavirus, vaccination, Neutralizing antibodies, Infection, memory, Antigen, vaccine dose, T cell, response, phenotype, CD4+ T cells, receptor, recall, CD38, CD4+ T cell, Antibody titers, Primary infection, acute respiratory syndrome, overlap, circulating, iCoS, Memory responses, populations, Cell, secondary, robust, exhibited, contribute, the spike protein, elicit, increase in, induce, expressing, recalled, follicular, 【제목키워드】 memory, recall, CD4+ T cell, SARS-CoV-2 spike,