Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling

Yoshiki Akatsuka, Edus H. Warren, Anthony G. Brickner, Ming Tseh Lin, Ted Gooly, Paul J. Martin, John A. Hansen, Victor H. Engelhard, Stanley R. Riddell

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have identified a new HLA 0201-restricted minor histocompatibility antigen encoded by the KIAA0020 gene and recognized by CD8+ cytotoxic T cells (CTL) derived from a patient with chronic GVHD (Brickner et al, submitted). This antigen, termed HA-8, results from a proline (P) to arginine (R) substitution at position 149 of the KIAA0020 protein (position 1 of the antigenic epitope). Peptides containing both R and P at position1 bind HLA A201 when pulsed onto cells in vitro but expression of minigene construcis encoding these peptides demonstrated that only the peptide containing R is appropriately processed and transported into the endoplasmic reticulum. KIAA0020 is broadly expressed in tissues with the highest levels in lung and liver. A PCR-RFLP method for genotyping KIAA0020 was developed and a retrospective analysis was performed to evaluate the effect of HA-8 disparity on GVHD after HLA identical sibling transplant. Genomic DNA samples from 235 Caucasian donor/recipient pairs previously used for the analysis of HA-1 disparity (Tseng et al, Blood 94: 2911, 1999) were used for this study. All patients received methotrexate and cyclosporin for GVHD prophylaxis. Of 235 patients, 25 (10.6%) received an HA-8 incompatible transplant and 210 (89.4%) received an HA-8 compatible transplant. Grade II - IV acute GVHD occurred in 12 (48.0%) of the HA-8 incompatible and 45.2 % of the HA-8 compatible recipients (p =.79). Clinical or pathologi c chronic GVHD was diagnosed in 18/25 (72%) of incompatible recipients compared with 114/210 (54%) compatible recipients (p =.09). These results suggest a potential association of HA-8 disparity with cGVHD. An HLA A2/HA-8 tetramer has been constructed and s being used prospectively to identify HA-8 specific T cells in blood and tissues after allogeneic BMT.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART I
Publication statusPublished - 01-12-2000
Externally publishedYes

Fingerprint

Minor Histocompatibility Antigens
Transplantation (surgical)
Transplants
Graft vs Host Disease
Grafts
Siblings
T-cells
Transplantation
Bone Marrow
Peptides
Blood
Tissue
T-Lymphocytes
HLA-A2 Antigen
Proline
Methotrexate
Endoplasmic Reticulum
Restriction Fragment Length Polymorphisms
Liver
Cyclosporine

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Akatsuka, Y., Warren, E. H., Brickner, A. G., Lin, M. T., Gooly, T., Martin, P. J., ... Riddell, S. R. (2000). Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling. Blood, 96(11 PART I).
Akatsuka, Yoshiki ; Warren, Edus H. ; Brickner, Anthony G. ; Lin, Ming Tseh ; Gooly, Ted ; Martin, Paul J. ; Hansen, John A. ; Engelhard, Victor H. ; Riddell, Stanley R. / Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling. In: Blood. 2000 ; Vol. 96, No. 11 PART I.
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title = "Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling",
abstract = "We have identified a new HLA 0201-restricted minor histocompatibility antigen encoded by the KIAA0020 gene and recognized by CD8+ cytotoxic T cells (CTL) derived from a patient with chronic GVHD (Brickner et al, submitted). This antigen, termed HA-8, results from a proline (P) to arginine (R) substitution at position 149 of the KIAA0020 protein (position 1 of the antigenic epitope). Peptides containing both R and P at position1 bind HLA A201 when pulsed onto cells in vitro but expression of minigene construcis encoding these peptides demonstrated that only the peptide containing R is appropriately processed and transported into the endoplasmic reticulum. KIAA0020 is broadly expressed in tissues with the highest levels in lung and liver. A PCR-RFLP method for genotyping KIAA0020 was developed and a retrospective analysis was performed to evaluate the effect of HA-8 disparity on GVHD after HLA identical sibling transplant. Genomic DNA samples from 235 Caucasian donor/recipient pairs previously used for the analysis of HA-1 disparity (Tseng et al, Blood 94: 2911, 1999) were used for this study. All patients received methotrexate and cyclosporin for GVHD prophylaxis. Of 235 patients, 25 (10.6{\%}) received an HA-8 incompatible transplant and 210 (89.4{\%}) received an HA-8 compatible transplant. Grade II - IV acute GVHD occurred in 12 (48.0{\%}) of the HA-8 incompatible and 45.2 {\%} of the HA-8 compatible recipients (p =.79). Clinical or pathologi c chronic GVHD was diagnosed in 18/25 (72{\%}) of incompatible recipients compared with 114/210 (54{\%}) compatible recipients (p =.09). These results suggest a potential association of HA-8 disparity with cGVHD. An HLA A2/HA-8 tetramer has been constructed and s being used prospectively to identify HA-8 specific T cells in blood and tissues after allogeneic BMT.",
author = "Yoshiki Akatsuka and Warren, {Edus H.} and Brickner, {Anthony G.} and Lin, {Ming Tseh} and Ted Gooly and Martin, {Paul J.} and Hansen, {John A.} and Engelhard, {Victor H.} and Riddell, {Stanley R.}",
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Akatsuka, Y, Warren, EH, Brickner, AG, Lin, MT, Gooly, T, Martin, PJ, Hansen, JA, Engelhard, VH & Riddell, SR 2000, 'Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling', Blood, vol. 96, no. 11 PART I.

Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling. / Akatsuka, Yoshiki; Warren, Edus H.; Brickner, Anthony G.; Lin, Ming Tseh; Gooly, Ted; Martin, Paul J.; Hansen, John A.; Engelhard, Victor H.; Riddell, Stanley R.

In: Blood, Vol. 96, No. 11 PART I, 01.12.2000.

Research output: Contribution to journalArticle

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T1 - Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling

AU - Akatsuka, Yoshiki

AU - Warren, Edus H.

AU - Brickner, Anthony G.

AU - Lin, Ming Tseh

AU - Gooly, Ted

AU - Martin, Paul J.

AU - Hansen, John A.

AU - Engelhard, Victor H.

AU - Riddell, Stanley R.

PY - 2000/12/1

Y1 - 2000/12/1

N2 - We have identified a new HLA 0201-restricted minor histocompatibility antigen encoded by the KIAA0020 gene and recognized by CD8+ cytotoxic T cells (CTL) derived from a patient with chronic GVHD (Brickner et al, submitted). This antigen, termed HA-8, results from a proline (P) to arginine (R) substitution at position 149 of the KIAA0020 protein (position 1 of the antigenic epitope). Peptides containing both R and P at position1 bind HLA A201 when pulsed onto cells in vitro but expression of minigene construcis encoding these peptides demonstrated that only the peptide containing R is appropriately processed and transported into the endoplasmic reticulum. KIAA0020 is broadly expressed in tissues with the highest levels in lung and liver. A PCR-RFLP method for genotyping KIAA0020 was developed and a retrospective analysis was performed to evaluate the effect of HA-8 disparity on GVHD after HLA identical sibling transplant. Genomic DNA samples from 235 Caucasian donor/recipient pairs previously used for the analysis of HA-1 disparity (Tseng et al, Blood 94: 2911, 1999) were used for this study. All patients received methotrexate and cyclosporin for GVHD prophylaxis. Of 235 patients, 25 (10.6%) received an HA-8 incompatible transplant and 210 (89.4%) received an HA-8 compatible transplant. Grade II - IV acute GVHD occurred in 12 (48.0%) of the HA-8 incompatible and 45.2 % of the HA-8 compatible recipients (p =.79). Clinical or pathologi c chronic GVHD was diagnosed in 18/25 (72%) of incompatible recipients compared with 114/210 (54%) compatible recipients (p =.09). These results suggest a potential association of HA-8 disparity with cGVHD. An HLA A2/HA-8 tetramer has been constructed and s being used prospectively to identify HA-8 specific T cells in blood and tissues after allogeneic BMT.

AB - We have identified a new HLA 0201-restricted minor histocompatibility antigen encoded by the KIAA0020 gene and recognized by CD8+ cytotoxic T cells (CTL) derived from a patient with chronic GVHD (Brickner et al, submitted). This antigen, termed HA-8, results from a proline (P) to arginine (R) substitution at position 149 of the KIAA0020 protein (position 1 of the antigenic epitope). Peptides containing both R and P at position1 bind HLA A201 when pulsed onto cells in vitro but expression of minigene construcis encoding these peptides demonstrated that only the peptide containing R is appropriately processed and transported into the endoplasmic reticulum. KIAA0020 is broadly expressed in tissues with the highest levels in lung and liver. A PCR-RFLP method for genotyping KIAA0020 was developed and a retrospective analysis was performed to evaluate the effect of HA-8 disparity on GVHD after HLA identical sibling transplant. Genomic DNA samples from 235 Caucasian donor/recipient pairs previously used for the analysis of HA-1 disparity (Tseng et al, Blood 94: 2911, 1999) were used for this study. All patients received methotrexate and cyclosporin for GVHD prophylaxis. Of 235 patients, 25 (10.6%) received an HA-8 incompatible transplant and 210 (89.4%) received an HA-8 compatible transplant. Grade II - IV acute GVHD occurred in 12 (48.0%) of the HA-8 incompatible and 45.2 % of the HA-8 compatible recipients (p =.79). Clinical or pathologi c chronic GVHD was diagnosed in 18/25 (72%) of incompatible recipients compared with 114/210 (54%) compatible recipients (p =.09). These results suggest a potential association of HA-8 disparity with cGVHD. An HLA A2/HA-8 tetramer has been constructed and s being used prospectively to identify HA-8 specific T cells in blood and tissues after allogeneic BMT.

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