Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics

Abstract

The human leukocyte antigen (HLA)-bound-viral antigens serve as an immunological signature that can be selectively recognized by T cells. As viruses evolve by acquiring mutations, it is essential to identify a range of viral presented antigens. Utilizing HLA-peptidomics we were able to identify SARS-CoV-2-derived peptides presented by highly prevalent HLA Class-I (HLA-I) molecules using infected cells as well as overexpression of SARS-CoV-2 genes. We found 26 HLA-I peptides and 36 HLA class-II (HLA-II) peptides. Among the identified peptides some were shared between different cells and some were derived from out-of-frame-ORFs. Seven of these peptides were previously shown to be immunogenic, and we identify two additional immuno-reactive peptides using HLA-multimer staining. These results may aid the development of the next generation of SARS-CoV-2 vaccines based on viral-specific-presented antigens that span several of the viral genes.

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

“…TGSNVFQTR from spike glycoprotein (638-646) was predicted binding to A*68:01 allele and it locates within the SD1 domain. ITFGGPSDSTGSNQNGER from nucelocapsid protein (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) was also identified in this study and has been predicted to bind to the same allele. Additionally, two class II peptides from nucleocapisd protein SPDDQIGYYRRATRRIR and FSKQLQQSMSSADSTQA were identified, which has not been reported before.…”

“…Host cells infected by the coronavirus is the simplest model to study the mechanism of viral infection and its impact on the immune system for the development of vaccines and therapeutics. Although several immunopeptidomics and proteomics studies of SARS-Cov-2 infected cells have been reported 19,[23][24][25][26]36 , there is not yet a study that integrated both immunopeptidomics and proteomics, including PTM targeted subomics. Thus, we developed a workflow that included immunopeptidomcis, proteomics, glycoproteomics, phosphoproteomcis and HLA targeted interactomics to provide with a comprehensive overall view of how host cells response to infection that may attribute to the pathology of Covid-19.…”

“…Several studies used different cell lines and techniques to study the change in either global proteome or PTM specific subproteome to identify the pathways involved in response to viral infection and develop therapeutics against Covid-19 [21][22][23][24][25] . However, immunopeptidomics were not included in those studies while the host proteome change was not studied in depth from several immunopeptidomics analysis 19,26,27 . As shown in recent studies, SARS-Cov-2 infection will hijack the antigen presentation pathways and prevent infected cells from presenting viral antigens 28,29 , which might cause the impaired T cell response in Covid-19 patients 30 .…”

An update on SARS-CoV-2 and dentistry

“…The transition between innate and adaptive immune response is central to the clinical progression of SARS-CoV-2 infection [10] and the destruction of lung cells triggers a local immune response, recruiting infection-responsive macrophages and monocytes, release cytokines and activate adaptive T-and Bcell immune responses [11] , as well as the release of interleukin (IL)-1β and IL-18, which contribute to the pathogenic inflammation responsible for the severity of COVID-19 symptoms [12] . Viral antigens bound to human leukocyte antigen (HLA) serve as an immune signature that can be selectively recognized by T cells [13] . Protective and harmful HLA variants have been described in both mild and severe forms of the disease, but considering the large number of existing variants, the data collected in such a short time span are to some extent confusing and contradictory [14] .…”

Cellular immunity in patients with COVID-19: molecular biology, pathophysiology, and clinical implications

“…Это позволяет выбрать клоны Т-клеток с наиболее желаемыми свойствами и генерировать антиген-специфичные трансгенные Т-клетки [48]. Кроме того, иммунодоминантные пептиды могут быть получены из последовательностей с открытой рамкой считывания, которые не захватываются современными схемами вакцинации [33,49].…”