Exploring the pre-immune landscape of antigen-specific T cells

Background Adaptive immune responses to newly encountered pathogens depend on the mobilization of antigen-specific clonotypes from a vastly diverse pool of naive T cells. Using recent advances in immune repertoire sequencing technologies, models of the immune receptor rearrangement process, and a da...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Genome medicine Ročník 10; číslo 1; s. 68 - 14
Hlavní autoři:	Pogorelyy, Mikhail V., Fedorova, Alla D., McLaren, James E., Ladell, Kristin, Bagaev, Dmitri V., Eliseev, Alexey V., Mikelov, Artem I., Koneva, Anna E., Zvyagin, Ivan V., Price, David A., Chudakov, Dmitry M., Shugay, Mikhail
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 25.08.2018 BioMed Central Ltd Springer Nature B.V BMC
Témata:	Adaptive immunity Ankylosing spondylitis Antigen Antigens Bioinformatics Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Computer applications Cord blood Cytomegalovirus Epitopes Epitopes - immunology Estimates Genetic aspects Genomics of Infection and Immunity Histocompatibility antigen HLA Histocompatibility Antigens Class I - immunology Human Genetics Humans Immune repertoire Immune system Immunogenicity Lymphocytes Lymphocytes T Medicine/Public Health Metabolomics Models, Statistical Multiculturalism & pluralism Pathogens Peptides - immunology Physicochemical properties Receptors, Antigen, T-Cell - immunology Systems Biology T cell receptor T cell receptors T cells T-Lymphocytes - immunology Umbilical cord Antigen T cell receptor Immunogenicity Immune repertoire
ISSN:	1756-994X, 1756-994X
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Background Adaptive immune responses to newly encountered pathogens depend on the mobilization of antigen-specific clonotypes from a vastly diverse pool of naive T cells. Using recent advances in immune repertoire sequencing technologies, models of the immune receptor rearrangement process, and a database of annotated T cell receptor (TCR) sequences with known specificities, we explored the baseline frequencies of T cells specific for defined human leukocyte antigen (HLA) class I-restricted epitopes in healthy individuals. Methods We used a database of TCR sequences with known antigen specificities and a probabilistic TCR rearrangement model to estimate the baseline frequencies of TCRs specific to distinct antigens epitopespecificT-cells. We verified our estimates using a publicly available collection of TCR repertoires from healthy individuals. We also interrogated a database of immunogenic and non-immunogenic peptides is used to link baseline T-cell frequencies with epitope immunogenicity. Results Our findings revealed a high degree of variability in the prevalence of T cells specific for different antigens that could be explained by the physicochemical properties of the corresponding HLA class I-bound peptides. The occurrence of certain rearrangements was influenced by ancestry and HLA class I restriction, and umbilical cord blood samples contained higher frequencies of common pathogen-specific TCRs. We also identified a quantitative link between specific T cell frequencies and the immunogenicity of cognate epitopes presented by defined HLA class I molecules. Conclusions Our results suggest that the population frequencies of specific T cells are strikingly non-uniform across epitopes that are known to elicit immune responses. This inference leads to a new definition of epitope immunogenicity based on specific TCR frequencies, which can be estimated with a high degree of accuracy in silico, thereby providing a novel framework to integrate computational and experimental genomics with basic and translational research efforts in the field of T cell immunology.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1756-994X 1756-994X
DOI:	10.1186/s13073-018-0577-7