Characterization of SARS-CoV-2 and common cold coronavirus-specific T cell responses in MIS-C and Kawasaki disease children

Hsieh, Li-En; Grifoni, Alba; Sidney, John; Shimizu, Chisato; Shike, Hiroko; Ramchandar, Nanda; Moreno, Elizabeth; Tremoulet, Adriana H; Burns, Jane C; Franco, Alessandra

The immunopathogenesis of multisystem inflammatory syndrome (MIS-C) in children that may follow exposure to SARS-CoV-2 is incompletely understood. Here, we studied SARS-CoV-2-specific T cells in MIS-C, Kawasaki disease (KD), and SARS-CoV-2 convalescent controls using peptide pools derived from SARS-CoV-2 spike or non-spike proteins, and common cold coronaviruses (CCC). Coordinated CD4+ and CD8+ SARS-CoV-2-specific T cells were detected in five MIS-C subjects with cross-reactivity to CCC. CD4+ and CD8+ T cell responses alone were documented in three and one subjects, respectively. T cell specificities in MIS-C did not correlate with disease severity and were similar to SARS-CoV-2 convalescent controls. T cell memory and cross-reactivity to CCC in MIS-C and SARS-CoV-2 convalescent controls were also similar. The chemokine receptor CCR6, but not CCR9, was highly expressed on SARS-CoV-2-specific CD4+ but not CD8+ T cells. Only two of 10 KD subjects showed a T cell response to CCC. Enumeration of myeloid antigen presenting cells revealed low cell precursors in MIS-C subjects compared to KD. In summary, children with MIS-C mount a normal T cell response to SARS-CoV-2 with no apparent relationship to antecedent CCC exposure. Low numbers of tolerogenic myeloid dendritic cells may impair their anti-inflammatory response. This article is protected by copyright. All rights reserved.