The HLA-A*0201-restricted minor histocompatibility antigen HA-1H peptide can also be presented by another HLA-A2 subtype, A*0206

Torikai, Hiroki; Akatsuka, Yoshiki; Miyauchi, Haruna; Terakura, Seitaro; Onizuka, Makoto; Tsujimura, Kunio; Miyamura, Koichi; Morishima, Yasuo; Kodera, Yoshihisa; Kuzushima, Kiyotaka; Takahashi, Toshitada

doi:10.1038/sj.bmt.1705689

Cited by 28 publications

(21 citation statements)

References 38 publications

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“…These PD-L1 [11][12][13][14][15][16][17][18][19] (TYWHLLNAF) and PD-L1 41-50 (KFPVEKQLDL) peptides are completely compatible with the predicted motif of amino acids binding to HLA-A24 molecules; Y or F residue at amino acid position 2 and L, F, I, or W residue at position 9. 23,24 These lines of evidence indicate that these PD-L1 peptides would be applicable as peptide-based anticancer vaccine for HLA-A24 + RCC patients. However, these results may not be completely representative of the in vivo immunogenicity of the peptide, and its true immunogenicity in patients can be determined only through clinical trials.…”

Section: Discussionmentioning

confidence: 97%

Identification of Programmed Death Ligand 1–derived Peptides Capable of Inducing Cancer-reactive Cytotoxic T Lymphocytes From HLA-A24+ Patients With Renal Cell Carcinoma

Minami

Shimizu

et al. 2015

Journal of Immunotherapy

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Molecular therapy targeting tumor angiogenesis has been the standard treatment for metastatic renal cell carcinoma (mRCC). However, despite their significant antitumor effects, most of patients with mRCC have not been cured. Under such circumstances, anticancer immunotherapy has been considered a promising treatment modality for mRCC, and cancer-reactive cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells. However, anticancer CTLs can be inhibited by several immune inhibitory mechanisms, including the interaction between programmed death 1 (PD-1) and its ligand PD-L1, on T cells and cancer cells, respectively. Alternatively, this also means that PD-L1 could be a promising target for anticancer immunotherapy. Therefore, we searched for PD-L1-derived peptides that are applicable for anticancer vaccine for HLA-A24(+) RCC patients. Among 5 peptides derived from PD-L1, which were prepared based on the binding motif to the HLA-A24(+) allele, both PD-L1(11-19) and PD-L1(41-50) peptides induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Such PD-L1 peptide-stimulated CD8 T cells showed cytotoxicity against HLA-A24(+) and PD-L1-expressing RCC cells. Although IFN-γ treatment increased PD-L1 expression on PD-L1(low) RCC cells, their sensitivity to cytotoxicity of PD-L1 peptide-stimulated CD8(+) T cells varied between patients. Altogether, these results indicate that both PD-L1(11-19) and PD-L1(41-50) peptides could be candidates for peptide-based anticancer vaccines for HLA-A24(+) mRCC patients.

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Section: Discussionmentioning

confidence: 97%

Identification of Programmed Death Ligand 1–derived Peptides Capable of Inducing Cancer-reactive Cytotoxic T Lymphocytes From HLA-A24+ Patients With Renal Cell Carcinoma

Minami

Shimizu

et al. 2015

Journal of Immunotherapy

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“…HA-1-specific CTL have been identified in PBMC samples obtained from patients who have received DLI without experiencing severe GVHD 30, 57, 60–61. However, analysis of transplant outcome based on donor/recipient disparity of HA-1 has provided conflicting data concerning a potential role of HA-1 in GVHD 62–64.…”

Section: Rationale For Targeting Lineage-restricted Minor H Antigens mentioning

confidence: 99%

Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia

2011

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Minor histocompatibility (H) antigens are major targets of a graft-versus-leukemia (GVL) effect mediated by donor CD8 + and CD4 + T cells following allogeneic hematopoietic cell transplantation (HCT) between human leukocyte antigen identical individuals. In the 15 years since the first molecular characterization of human minor H antigens, significant strides in minor H antigen discovery have been made as a consequence of advances in cellular, genetic and molecular techniques. Much has been learned about the mechanisms of minor H antigen immunogenicity, their expression on normal and malignant cells, and their role in GVL responses. T cells specific for minor H antigens expressed on leukemic cells, including leukemic stem cells, can be isolated and expanded in vitro and infused into allogeneic HCT recipients to augment the GVL effect to prevent and treat relapse. The first report of the adoptive transfer of minor H antigen-specific T-cell clones to patients with leukemic relapse in 2010 illustrates the potential for the manipulation of alloreactivity for therapeutic benefit. This review describes the recent developments in T-cell recognition of human minor H antigens, and efforts to translate these discoveries to reduce leukemia relapse after allogeneic HCT.

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“…HA-1 is antigenic due to a single nucleotide polymorphism in which the arginine in the peptide sequence KECVL R DDLLEA is changed to a histidine, giving rise to the immunogenic peptide KECVL H DDLLEA. This single nucleotide polymorphism results in increased binding affinity of the peptide to the appropriate major histocompatibility complex (MHC) for immune recognition, in this case HLA-A*0201, A*0206, B*60 or B*40012 [24–28]. HA-1-specific CD8+ T cells have been identified in human pregnancies in which an HLA-A2-positive mother expresses the non-immunogenic form of the peptide and the fetus expresses the immunogenic form [13].…”

Section: Introductionmentioning

confidence: 99%

Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women

et al. 2015

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Introduction Maternal T-cells reactive towards paternally inherited fetal minor histocompatibility antigens are expanded during pregnancy. Placental trophoblast cells express at least four fetal antigens, including human minor histocompatibility antigen 1 (HA-1). We investigated oxygen as a potential regulator of HA-1 and whether HA-1 expression is altered in preeclamptic placentas. Methods Expression and regulation of HA-1 mRNA and protein were examined by qRT-PCR and immunohistochemistry, using first, second, and third trimester placentas, first trimester placental explant cultures, and term purified cytotrophoblast cells. Low oxygen conditions were achieved by varying ambient oxygen, and were mimicked using cobalt chloride. HA-1 mRNA and protein expression levels were evaluated in preeclamptic and control placentas. Results HA-1 protein expression was higher in the syncytiotrophoblast of first trimester as compared to second trimester and term placentas (P<0.01). HA-1 mRNA was increased in cobalt chloride-treated placental explants and purified cytotrophoblast cells (P=0.04 and P<0.01, respectively) and in purified cytotrophoblast cells cultured under 2% as compared to 8% and 21% oxygen (P<0.01). HA-1 mRNA expression in preeclamptic vs. control placentas was increased 3.3-fold (P=0.015). HA-1 protein expression was increased in syncytial nuclear aggregates and the syncytiotrophoblast of preeclamptic vs. control placentas (P= 0.02 and 0.03, respectively). Discussion Placenta HA-1 expression is regulated by oxygen and is increased in the syncytial nuclear aggregates and syncytiotrophoblast of preeclamptic as compared to control placentas. Increased HA-1 expression, combined with increased preeclamptic syncytiotrophoblast deportation, provides a novel potential mechanism for exposure of the maternal immune system to increased fetal antigenic load during preeclampsia.

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The HLA-A0201-restricted minor histocompatibility antigen HA-1H peptide can also be presented by another HLA-A2 subtype, A0206

Cited by 28 publications

References 38 publications

Identification of Programmed Death Ligand 1–derived Peptides Capable of Inducing Cancer-reactive Cytotoxic T Lymphocytes From HLA-A24+ Patients With Renal Cell Carcinoma

Identification of Programmed Death Ligand 1–derived Peptides Capable of Inducing Cancer-reactive Cytotoxic T Lymphocytes From HLA-A24+ Patients With Renal Cell Carcinoma

Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia

Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women

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