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

H. Torikai, Yoshiki Akatsuka, H. Miyauchi, S. Terakura, M. Onizuka, K. Tsujimura, K. Miyamura, Y. Morishima, Y. Kodera, K. Kuzushima, T. Takahashi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

HA-1H is one of the most attractive minor histocompatibility antigens (mHA) as a target for immunotherapy of hematopoietic malignancies, but HLA-A*0201 and HLA-B60 molecules capable of presenting HA-1H-derived peptides are less common in eastern Asian populations when compared with Caucasian populations. Therefore, an attempt was made to search for novel epitopes presented by HLA alleles other than those previously reported by generating CTL lines from patients undergoing HLA-identical, HA-1 disparate hematopoietic stem cell transplantation (hematopoietic SCT) by stimulation with a 29-mer HA-1H peptide spanning a central polymorphic histidine (His). Two CTL clones established were found to be restricted by HLA-A*0206, which is the second or third most common HLA-A2 subtype worldwide. Epitope mapping revealed that the clones recognized the same nonameric peptide as A*0201-restricted HA-1H, VLHDDLLEA. This epitope was unexpected, since it does not contain any preferred anchor motifs for HLA-A*0206. However, an HLA peptide binding assay revealed stronger binding of this peptide to A*0206 than to A*0201. Interestingly, HLA-A* 0206-restricted CTL clones could lyse both HLA-A*0206+ and HLA-A*0201+ targets (including leukemic blasts) that express HA-1H peptide endogenously, whereas an HLA-A*0201-restricted, HA-1H-specific CTL clone failed to lyse HLA-A*0206+ targets. This finding will expand the patient population who can benefit from HA-1H -based immunotherapy.

Original languageEnglish
Pages (from-to)165-174
Number of pages10
JournalBone Marrow Transplantation
Volume40
Issue number2
DOIs
Publication statusPublished - 01-07-2007
Externally publishedYes

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Minor Histocompatibility Antigens
HLA-A2 Antigen
HLA-A Antigens
Peptides
Clone Cells
Immunotherapy
Epitopes
Population
Epitope Mapping
Hematopoietic Stem Cell Transplantation
Hematologic Neoplasms
Histidine
HLA-A*02:01 antigen
Alleles

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Torikai, H. ; Akatsuka, Yoshiki ; Miyauchi, H. ; Terakura, S. ; Onizuka, M. ; Tsujimura, K. ; Miyamura, K. ; Morishima, Y. ; Kodera, Y. ; Kuzushima, K. ; Takahashi, T. / The HLA-A *0201-restricted minor histocompatibility antigen HA-1H peptide can also be presented by another HLA-A2 subtype, A *0206. In: Bone Marrow Transplantation. 2007 ; Vol. 40, No. 2. pp. 165-174.
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abstract = "HA-1H is one of the most attractive minor histocompatibility antigens (mHA) as a target for immunotherapy of hematopoietic malignancies, but HLA-A*0201 and HLA-B60 molecules capable of presenting HA-1H-derived peptides are less common in eastern Asian populations when compared with Caucasian populations. Therefore, an attempt was made to search for novel epitopes presented by HLA alleles other than those previously reported by generating CTL lines from patients undergoing HLA-identical, HA-1 disparate hematopoietic stem cell transplantation (hematopoietic SCT) by stimulation with a 29-mer HA-1H peptide spanning a central polymorphic histidine (His). Two CTL clones established were found to be restricted by HLA-A*0206, which is the second or third most common HLA-A2 subtype worldwide. Epitope mapping revealed that the clones recognized the same nonameric peptide as A*0201-restricted HA-1H, VLHDDLLEA. This epitope was unexpected, since it does not contain any preferred anchor motifs for HLA-A*0206. However, an HLA peptide binding assay revealed stronger binding of this peptide to A*0206 than to A*0201. Interestingly, HLA-A* 0206-restricted CTL clones could lyse both HLA-A*0206+ and HLA-A*0201+ targets (including leukemic blasts) that express HA-1H peptide endogenously, whereas an HLA-A*0201-restricted, HA-1H-specific CTL clone failed to lyse HLA-A*0206+ targets. This finding will expand the patient population who can benefit from HA-1H -based immunotherapy.",
author = "H. Torikai and Yoshiki Akatsuka and H. Miyauchi and S. Terakura and M. Onizuka and K. Tsujimura and K. Miyamura and Y. Morishima and Y. Kodera and K. Kuzushima and T. Takahashi",
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Torikai, H, Akatsuka, Y, Miyauchi, H, Terakura, S, Onizuka, M, Tsujimura, K, Miyamura, K, Morishima, Y, Kodera, Y, Kuzushima, K & Takahashi, T 2007, 'The HLA-A *0201-restricted minor histocompatibility antigen HA-1H peptide can also be presented by another HLA-A2 subtype, A *0206', Bone Marrow Transplantation, vol. 40, no. 2, pp. 165-174. https://doi.org/10.1038/sj.bmt.1705689

The HLA-A *0201-restricted minor histocompatibility antigen HA-1H peptide can also be presented by another HLA-A2 subtype, A *0206. / Torikai, H.; Akatsuka, Yoshiki; Miyauchi, H.; Terakura, S.; Onizuka, M.; Tsujimura, K.; Miyamura, K.; Morishima, Y.; Kodera, Y.; Kuzushima, K.; Takahashi, T.

In: Bone Marrow Transplantation, Vol. 40, No. 2, 01.07.2007, p. 165-174.

Research output: Contribution to journalArticle

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T1 - The HLA-A *0201-restricted minor histocompatibility antigen HA-1H peptide can also be presented by another HLA-A2 subtype, A *0206

AU - Torikai, H.

AU - Akatsuka, Yoshiki

AU - Miyauchi, H.

AU - Terakura, S.

AU - Onizuka, M.

AU - Tsujimura, K.

AU - Miyamura, K.

AU - Morishima, Y.

AU - Kodera, Y.

AU - Kuzushima, K.

AU - Takahashi, T.

PY - 2007/7/1

Y1 - 2007/7/1

N2 - HA-1H is one of the most attractive minor histocompatibility antigens (mHA) as a target for immunotherapy of hematopoietic malignancies, but HLA-A*0201 and HLA-B60 molecules capable of presenting HA-1H-derived peptides are less common in eastern Asian populations when compared with Caucasian populations. Therefore, an attempt was made to search for novel epitopes presented by HLA alleles other than those previously reported by generating CTL lines from patients undergoing HLA-identical, HA-1 disparate hematopoietic stem cell transplantation (hematopoietic SCT) by stimulation with a 29-mer HA-1H peptide spanning a central polymorphic histidine (His). Two CTL clones established were found to be restricted by HLA-A*0206, which is the second or third most common HLA-A2 subtype worldwide. Epitope mapping revealed that the clones recognized the same nonameric peptide as A*0201-restricted HA-1H, VLHDDLLEA. This epitope was unexpected, since it does not contain any preferred anchor motifs for HLA-A*0206. However, an HLA peptide binding assay revealed stronger binding of this peptide to A*0206 than to A*0201. Interestingly, HLA-A* 0206-restricted CTL clones could lyse both HLA-A*0206+ and HLA-A*0201+ targets (including leukemic blasts) that express HA-1H peptide endogenously, whereas an HLA-A*0201-restricted, HA-1H-specific CTL clone failed to lyse HLA-A*0206+ targets. This finding will expand the patient population who can benefit from HA-1H -based immunotherapy.

AB - HA-1H is one of the most attractive minor histocompatibility antigens (mHA) as a target for immunotherapy of hematopoietic malignancies, but HLA-A*0201 and HLA-B60 molecules capable of presenting HA-1H-derived peptides are less common in eastern Asian populations when compared with Caucasian populations. Therefore, an attempt was made to search for novel epitopes presented by HLA alleles other than those previously reported by generating CTL lines from patients undergoing HLA-identical, HA-1 disparate hematopoietic stem cell transplantation (hematopoietic SCT) by stimulation with a 29-mer HA-1H peptide spanning a central polymorphic histidine (His). Two CTL clones established were found to be restricted by HLA-A*0206, which is the second or third most common HLA-A2 subtype worldwide. Epitope mapping revealed that the clones recognized the same nonameric peptide as A*0201-restricted HA-1H, VLHDDLLEA. This epitope was unexpected, since it does not contain any preferred anchor motifs for HLA-A*0206. However, an HLA peptide binding assay revealed stronger binding of this peptide to A*0206 than to A*0201. Interestingly, HLA-A* 0206-restricted CTL clones could lyse both HLA-A*0206+ and HLA-A*0201+ targets (including leukemic blasts) that express HA-1H peptide endogenously, whereas an HLA-A*0201-restricted, HA-1H-specific CTL clone failed to lyse HLA-A*0206+ targets. This finding will expand the patient population who can benefit from HA-1H -based immunotherapy.

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