HLA‐dependent variation in SARS‐CoV‐2 CD8 ⁺ T cell cross‐reactivity with human coronaviruses

Abstract

The conditions and extent of cross‐protective immunity between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and common‐cold human coronaviruses (HCoVs) remain open despite several reports of pre‐existing T cell immunity to SARS‐CoV‐2 in individuals without prior exposure. Using a pool of functionally evaluated SARS‐CoV‐2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC‐presented peptides from at least one HCoV. Employing this map of SARS‐CoV‐2‐non‐homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID‐19 patients. After combining our map with SARS‐CoV‐2‐specific TCR repertoire data from COVID‐19 patients and healthy controls, we show that public repertoires for the majority of convalescent patients are dominated by TCRs cognate to non‐homologous SARS‐CoV‐2 peptides. We find that for a subset of patients, >50% of their public SARS‐CoV‐2‐specific repertoires consist of TCRs cognate to homologous SARS‐CoV‐2‐HCoV peptides. Further analysis suggests that this skewed distribution of TCRs cognate to homologous or non‐homologous peptides in COVID‐19 patients is likely to be HLA‐dependent. Finally, we provide 10 SARS‐CoV‐2 peptides with known cognate TCRs that are conserved across multiple coronaviruses and are predicted to be recognized by a high proportion of the global population. These findings may have important implications for COVID‐19 heterogeneity, vaccine‐induced immune responses, and robustness of immunity to SARS‐CoV‐2 and its variants.

Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19

“…This discrepancy could come from the difference in the epitope preference of each HLA haplotype since our study focused on HLA-A * 24:02. Additionally, the other papers identified cross-reactive T cells present prior to the COVID-19 pandemic in their cohorts 52 , 53 , which we could not detect in our cohort. It could also influence the memory T cell pool in the convalescents and could affect the screening results, accordingly.…”

Genome‐wide association studies of response and side effects to the BNT162b2 vaccine in Italian healthcare workers: Increased antibody levels and side effects in carriers of the HLA‐A*03:01 allele

“…However, a possible explanation of the association between HLA‐A*03:01 and high antibody titers could be sought in the CD8+ T cells SARS‐CoV‐2‐HCoV cross‐reactivity conditioned by this allele. In fact, in a recent study, Buckley and colleagues propose that subjects possessing some HLA alleles, including the HLA‐A*03:01 allele, are more likely to have SARS‐CoV‐2‐HCoV cross‐reactive CD8+ T cells if they have previously been exposed to endemic coronaviruses 47 . The subjects analyzed in this study are all healthcare workers and, according to the World Health Organization, respiratory infections are among the most common occupational infections in this category of workers.…”

“…In fact, in a recent study, Buckley and colleagues propose that subjects possessing some HLA alleles, including the HLA-A*03:01 allele, are more likely to have SARS-CoV-2-HCoV cross-reactive CD8+ T cells if they have previously been exposed to endemic coronaviruses. 47 The subjects analyzed in this study are all healthcare workers and, according to the World Health Organization, respiratory infections are among the most common occupational infections in this category of workers. Therefore, we hypothesize that the association between the HLA-A*03:01 allele and high antibody levels observed in our study may be attributed to the fact that the examined individuals are more likely to have been exposed to endemic coronaviruses in the past.…”

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID

“…However, it might be possible that these Tregs are advantageous, regulating a cytokine storm that would not have been as bad without their extraordinary contribution. In context to this, a recent investigation on CD8+ T cells from the same patients revealed a lack of SARS-CoV2-reactive cells in the blood throughout the acute stage, which supports this theory [ 51 , 99 ]. However, in the absence of FoxP3 expression, Tregs have been shown to have pro-inflammatory properties [ 100 ], which can be detrimental.…”