IN SILICO ANALYSIS OF T-CELL RECEPTORS SPECIFIC TO THE MINOR HISTOCOMPATIBILITY ANTIGEN HA-2

S. A. Sheetikov; Шитиков С. А.; A. A. Kuchmiy; Кучмий А. А.; N. A. Bykova; Быкова Н. А.; S. Yu. Filkin; Филькин С. Ю.; D. S. Romaniuk; Романюк Д. С.; G. A. Efimov; Ефимов Г. А.

doi:10.31857/S102872210005018-4

IN SILICO ANALYSIS OF T-CELL RECEPTORS SPECIFIC TO THE MINOR HISTOCOMPATIBILITY ANTIGEN HA-2

Authors: Sheetikov S.A.¹^,2, Kuchmiy A.A.¹, Bykova N.A.¹, Filkin S.Y.¹, Romaniuk D.S.¹, Efimov G.A.¹^,2
Affiliations:
1. National Research Center for Hematology, Russian Academy of Medical Sciences (HSC)
2. Lomonosov Moscow State University
Issue: Vol 22, No 1 (2019)
Pages: 31-43
Section: ORIGINAL ARTICLES
URL: https://journal-vniispk.ru/1028-7221/article/view/119333
DOI: https://doi.org/10.31857/S102872210005018-4
ID: 119333

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Abstract

Hematopoietic stem cells transplantation of (HSCT) from the related or unrelated donor is used as a treatment for hematopoietic system malignancies. However, transplantation triggers an immune response of the donor cells to the recipient’s antigens. The response to the healthy tissues is called a graft versus host reaction (GVHD), and the response to the hematopoietic tissue in the context of malignant disease is called a graft versus leukemia (GVL) eff ect. The development of GVL reactivity is a favorable consequence of transplantation, since it eliminates residual tumor cells and prevents the relapse. It was demonstrated that immune response arises towards polymorphic peptides, presented in the molecules of the major histocompatibility complex (HLA). Such peptides are derived from the proteasomal degradation of proteins expressed from the genes with non-synonymous single nucleotide polymorphisms and are referred to as minor histocompatibility antigens (MiHA). Studying the structure of T- cell receptor (TCR) repertoires that recognize MiHAgs can help identify the mechanisms for the formation of the alloreactive response and is important for predicting the antigen of alloreactive clones with unknown specificity. In this article the genetic sequences encoding T-cell receptors specific to the HA-2 minor antigen were determined and analyzed in silico. We found the predominant use of the V21 and J42 segments in the formation of the CDR3 region of the α-chain and the presence of the V7-8 segment in most CDR3 β-chain regions, which indicates the existence of a conservative motif responsible for recognizing the HA-2 antigen.

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Russian Federation

References

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