High-throughput and single-cell T cell receptor sequencing technologies.
T cells express T cell receptors (TCRs) composed of somatically recombined TCRalpha and TCRbeta chains, which mediate recognition of major histocompatibility complex (MHC)-antigen complexes and drive the antigen-specific adaptive immune response to pathogens and cancer. The TCR repertoire in each individual is highly diverse, which allows for recognition of a wide array of foreign antigens, but also presents a challenge in analyzing this response using conventional methods. Recent studies have developed high-throughput sequencing technologies to identify TCR sequences, analyze their antigen specificities using experimental and computational tools, and pair TCRs with transcriptional and epigenetic cell state phenotypes in single cells. In this Review, we highlight these technological advances and describe how they have been applied to discover fundamental insights into T cell-mediated immunity.
View details for DOI 10.1038/s41592-021-01201-8
View details for PubMedID 34282327
Identification of presented SARS-CoV-2 HLA class I and HLA class II peptides using HLA peptidomics.
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 presented viral antigens. Using HLA peptidomics, we are able to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides presented by highly prevalent HLA class I (HLA-I) molecules by using infected cells as well as overexpression of SARS-CoV-2 genes. We find 26 HLA-I peptides and 36 HLA class II (HLA-II) peptides. Among the identified peptides, some are shared between different cells and some are derived from out-of-frame open reading frames (ORFs). Seven of these peptides were previously shown to be immunogenic, and we identify two additional immunoreactive peptides by using HLA multimer staining. These results may aid the development of the next generation of SARS-CoV-2 vaccines based on presented viral-specific antigens that span several of the viral genes.
View details for DOI 10.1016/j.celrep.2021.109305
View details for PubMedID 34166618
The Power of Single Cell Technologies; from T Cell Receptor to Antigen(s) in Multiple Sclerosis
WILEY. 2020: S198
View details for Web of Science ID 000572509100353