Concordance of B- and T-cell responses to SARS-CoV-2 infection, irrespective of symptoms suggestive of COVID-19.

This study assessed T-cell responses in individuals with and without a positive antibody response to SARS-CoV-2, in symptomatic and asymptomatic individuals during the COVID-19 pandemic. Participants were drawn from the TwinsUK cohort, grouped by (a) presence or absence of COVID-associated symptoms (S+, S-), logged prospectively through the COVID Symptom Study app, and (b) anti-IgG Spike and anti-IgG Nucleocapsid antibodies measured by ELISA (Ab+, Ab-), during the first wave of the UK pandemic. T-cell helper and regulatory responses after stimulation with SARS-CoV-2 peptides were assessed. Thirty-two participants were included in the final analysis. Fourteen of 15 with IgG Spike antibodies had a T-cell response to SARS-CoV-2-specific peptides; none of 17 participants without IgG Spike antibodies had a T-cell response (χ2 : 28.2, p < 0.001). Quantitative T-cell responses correlated strongly with fold-change in IgG Spike antibody titer (ρ = 0.79, p < 0.0001) but not to symptom score (ρ = 0.17, p = 0.35). Humoral and cellular immune responses to SARS-CoV-2 are highly correlated. We found no evidence of cellular immunity suggestive of SARS-CoV2 infection in individuals with a COVID-19-like illness but negative antibodies.

Mapping T Cell Responses to Native and Neo-Islet Antigen Epitopes in at Risk and Type 1 Diabetes Subjects.

Aims: Recent studies highlight the potentially important role of neoepitopes in breaking immune tolerance in type 1 diabetes. T cell reactivity to these neoepitopes has been reported, but how this response compares quantitatively and phenotypically with previous reports on native epitopes is not known. Thus, an understanding of the relationship between native and neoepitopes and their role as tolerance breakers or disease drivers in type 1 diabetes is required. We set out to compare T cell reactivity and phenotype against a panel of neo- and native islet autoantigenic epitopes to examine how this relates to stages of type 1 diabetes development. Methods: Fifty-four subjects comprising patients with T1D, and autoantibody-positive unaffected family members were tested against a panel of neo- and native epitopes by ELISPOT (IFN-γ, IL-10, and IL-17). A further subset of two patients was analyzed by Single Cell Immune Profiling (RNAseq and TCR α/ß) after stimulation with pools of native and neoepitope peptides. Results: T cell responses to native and neoepitopes were present in patients with type 1 diabetes and at-risk subjects, and overall, there were no significant differences in the frequency, magnitude, or phenotype between the two sets of peptide stimuli. Single cell RNAseq on responder T cells revealed a similar profile in T1D patients stimulated with either neo- or native epitopes. A pro-inflammatory gene expression profile (TNF-α, IFN-γ) was dominant in both native and neoepitope stimulated T cells. TCRs with identical clonotypes were found in T cell responding to both native and neoepitopes. Conclusion/Interpretation: These data suggest that in peripheral blood, T cell responses to both native and neoepitopes are similar in terms of frequency and phenotype in patients with type 1 diabetes and high-risk unaffected family members. Furthermore, using a combination of transcriptomic and clonotypic analyses, albeit using a limited panel of peptides, we show that neoepitopes are comparable to native epitopes currently in use for immune-monitoring studies.