In Silico Analysis of the Minor Histocompatibility Antigen Landscape Based on the 1000 Genomes Project

Frontiers in Immunology
Nadia A BykovaGrigory A Efimov

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is routinely used to treat hematopoietic malignancies. The eradication of residual tumor cells during engraftment is mediated by donor cytotoxic T lymphocytes reactive to alloantigens. In a HLA-matched transplantation context, alloantigens are encoded by various polymorphic genes situated outside the HLA locus, also called minor histocompatibility antigens (MiHAs). Recently, MiHAs have been recognized as promising targets for post-transplantation T-cell immunotherapy as they have several appealing advantages over tumor-associated antigens (TAAs) and neoantigens, i.e., they are more abundant than TAAs, which potentially facilitates multiple targeting; and unlike neoantigens, they are encoded by germline polymorphisms, some of which are common and thus, suitable for off-the-shelf therapy. The genetic sources of MiHAs are nonsynonymous polymorphisms that cause differences between the recipient and donor proteomes and subsequently, the immunopeptidomes. Systematic description of the alloantigen landscape in HLA-matched transplantation is still lacking as previous studies focused only on a few immunogenic and common MiHAs. Here, we perform a thorough in silico analysis o...Continue Reading

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Citations

Aug 29, 2019·Frontiers in Immunology·Sarah NersesianJeanette E Boudreau
Jul 6, 2019·Frontiers in Immunology·Dmitrii S RomaniukGrigory A Efimov
May 20, 2020·Frontiers in Immunology·Elizabeth Krieger, Amir Ahmed Toor
Jul 17, 2020·Frontiers in Immunology·Tuna MutisRobbert M Spaapen
Apr 20, 2021·Trends in Genetics : TIG·Pierre PontarottiJulien Paganini
Dec 7, 2021·Frontiers in Immunology·Paul J MartinJohn A Hansen

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Methods Mentioned

BETA
exome-sequencing
Genotyping
transgenic

Software Mentioned

netMHCpan
CrossMap
MixMHC
ENSEMBL
netMHCpan -

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