Downregulation of HLA class II is associated with relapse after allogeneic stem cell transplantation and alters recognition by antigen-specific T cells

Yoshitaka Adachi, Toshiyasu Sakai, Seitaro Terakura, Takashi Shiina, Shingo Suzuki, Hiroshi Hamana, Hiroyuki Kishi, Takehiko Sasazuki, Hisashi Arase, Ryo Hanajiri, Tatsunori Goto, Tetsuya Nishida, Makoto Murata, Hitoshi Kiyoi

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1 Citation (Scopus)

Abstract

Genomic deletion of donor–patient-mismatched HLA alleles in leukemic cells is a major cause of relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Mismatched HLA is frequently lost as an individual allele or a whole region in HLA-class I, however, it is downregulated in HLA-class II. We hypothesized that there might be a difference in T cell recognition capacity against epitopes associated with HLA-class I and HLA-class II and consequently such allogeneic immune pressure induced HLA alterations in leukemic cells. To investigate this, we conducted in vitro experiments with T cell receptor-transduced T (TCR-T) cells. The cytotoxic activity of NY-ESO-1-specific TCR-T cells exhibited similarly against K562 cells with low HLA-A*02:01 expression. However, we demonstrated that the cytokine production against low HLA-DPB1*05:01 expression line decreased gradually from the HLA expression level approximately 2-log lower than normal expressors. Using sort-purified leukemia cells before and after HSCT, we applied the next-generation sequencing, and revealed that there were several marked downregulations of HLA-class II alleles which demonstrated consistently low expression from pre-transplantation. The marked downregulation of HLA-class II may lead to decreased antigen recognition ability of antigen-specific T cells and may be one of immune evasion mechanism associated with HLA-class II downregulation.

Original languageEnglish
JournalInternational journal of hematology
DOIs
Publication statusAccepted/In press - 2022

All Science Journal Classification (ASJC) codes

  • Hematology

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