Biology subjects

Kovalchik, K.

Publications and source records attributed to Kovalchik, K..

3 recordsLinked to original sources

bioRxiv2022

Integrated Immunopeptidomics and Proteomics Study Reveals Imbalanced Innate and Adaptive Immune Responses to SARS-Cov-2 Infection

We present an integrated immunopeptidomics and proteomics study of SARS-Cov-2 infection to comprehensively decipher the changes in host cells in response to viral infection. Our results indicated that innate immune response in Calu-3 cells was initiated by TLR3, followed by activation of interferon signaling pathway. Host cells also present viral antigens to the cell surface through both Class I and Class II MHC system for recognition by adaptive immune system. SARS-Cov-2 infection led to the disruption of antigen presentation as demonstrated by higher level of HLA proteins from the flow-through of MHC immunoprecipitation. Glycosylation analysis of HLA proteins from the elution and flow-through of immunoprecipitation revealed that the synthesis and degradation of HLA protein was affected by SARS-Cov-2 infection. This study provided many useful information to study the host response to SARS-Cov-2 infection and would be helpful for the development of therapeutics and vaccine for Covid-19 and future pandemic.

immunology↗

bioRxiv2021

The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner

The rapid, global dispersion of SARS-CoV-2 since its initial identification in December 2019 has led to the emergence of a diverse range of variants. The initial concerns regarding the virus were quickly compounded with concerns relating to the impact of its mutated forms on viral infectivity, pathogenicity and immunogenicity. To address the latter, we seek to understand how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic, before mass vaccination. We analyzed a total of 330,246 high quality SARS-CoV-2 genome assemblies sampled across 143 countries and all major continents. Strikingly, we found that specific mutational patterns in SARS-CoV-2 diversify T cell epitopes in an HLA supertype-dependent manner. In fact, we observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family. In addition, we show that this predicted global loss of epitopes is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7 supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic. Together, our study lays the foundation to help understand how SARS-CoV-2 mutants shape the repertoire of T cell targets and T cell immunity across human populations. The proposed theoretical framework has implications in viral evolution, disease severity, vaccine resistance and herd immunity.

immunology↗

bioRxiv2020

The Global Architecture Shaping the Heterogeneity and Tissue-Dependency of the MHC Class I Immunopeptidome is Evolutionarily Conserved

Understanding the molecular principles that govern the composition of the mammalian MHC-I immunopeptidome (MHC-Ii) across different primary tissues is fundamentally important to predict how T cell respond in different contexts in vivo. Here, we performed a global analysis of the mammalian MHC-Ii from 29 and 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, -B and -C allotypes do not contribute evenly to the global composition of the MHC-Ii across multiple human tissues. Second, we found that peptides that are presented in a tissue-dependent and -independent manner share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-Ii at the organism-wide scale. Finally, we uncovered new components of the antigen processing and presentation network that may drive the high level of heterogeneity of the MHC-Ii across different tissues in mammals. This study opens up new avenues toward a system-wide understanding of antigen presentation in vivo and may serve as ground work to understand tissue-dependent T cell responses in autoimmunity, infectious diseases and cancer.

immunology↗