4.1 Article

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

Journal

INTERNATIONAL JOURNAL OF HEMATOLOGY
Volume 115, Issue 3, Pages 371-381

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s12185-021-03273-w

Keywords

HLA mismatch; Allogeneic hematopoietic stem cell transplantation; Graft-versus-host disease (GVHD); Graft-versus-leukemia effect (GVL); HLA class II downregulation; CTL recognition

Categories

Funding

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI [18k08351]
  2. Practical Research for Innovative Cancer Control [17ck0106291h0001]
  3. Practical Research Project for Allergic Diseases and Immunology from the Japan Agency for Medical Research and Development [19ek0510022h0003, 21ek0510032h0002]
  4. Grants-in-Aid for Scientific Research [18K08351] Funding Source: KAKEN

Ask authors/readers for more resources

Genomic deletion of donor-patient-mismatched HLA alleles in leukemic cells is a major cause of relapse after allogeneic hematopoietic stem cell transplantation. The downregulation of HLA II may lead to decreased antigen recognition ability of antigen-specific T cells and may be one of the immune evasion mechanisms.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.1
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available