Identification of a novel UTY-encoded minor histocompatibility antigen

TY - JOUR

T1 - Identification of a novel UTY-encoded minor histocompatibility antigen

AU - Mortensen, Bo Kok

AU - Rasmussen, Annika Hammershaimb

AU - Larsen, M.E.

AU - Larsen, M.V.

AU - Lund, O.

AU - Brændstrup, Peter

AU - Harndahl, Mikkel Nors

AU - Rasmussen, Michael

AU - Buus, Søren

AU - Buus, Anette Stryhn

AU - Vindeløv, Lars

N1 - © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

PY - 2012/8

Y1 - 2012/8

N2 - Minor histocompatibility antigens (mHags) encoded by the Y-chromosome (H-Y-mHags) are known to play a pivotal role in allogeneic haematopoietic cell transplantation (HCT) involving female donors and male recipients. We present a new H-Y-mHag, YYNAFHWAI (UTY(139-147)), encoded by the UTY gene and presented by HLA-A*24:02. Briefly, short peptide stretches encompassing multiple putative H-Y-mHags were designed using a bioinformatics predictor of peptide-HLA binding, NetMHCpan. These peptides were used to screen for peptide-specific HLA-restricted T cell responses in peripheral blood mononuclear cells obtained post-HCT from male recipients of female donor grafts. In one of these recipients, a CD8+ T cell response was observed against a peptide stretch encoded by the UTY gene. Another bioinformatics tool, HLArestrictor, was used to identify the optimal peptide and HLA-restriction element. Using peptide/HLA tetramers, the specificity of the CD8+ T cell response was successfully validated as being HLA-A*24:02-restricted and directed against the male UTY(139-147) peptide. Functional analysis of these T cells demonstrated male UTY(139-147) peptide-specific cytokine secretion (IFNγ, TNFα and MIP-1β) and cytotoxic degranulation (CD107a). In contrast, no responses were seen when the T cells were stimulated with patient tumour cells alone. CD8+ T cells specific for this new H-Y-mHag were found in three of five HLA-A*24:02-positive male recipients of female donor HCT grafts available for this study.

AB - Minor histocompatibility antigens (mHags) encoded by the Y-chromosome (H-Y-mHags) are known to play a pivotal role in allogeneic haematopoietic cell transplantation (HCT) involving female donors and male recipients. We present a new H-Y-mHag, YYNAFHWAI (UTY(139-147)), encoded by the UTY gene and presented by HLA-A*24:02. Briefly, short peptide stretches encompassing multiple putative H-Y-mHags were designed using a bioinformatics predictor of peptide-HLA binding, NetMHCpan. These peptides were used to screen for peptide-specific HLA-restricted T cell responses in peripheral blood mononuclear cells obtained post-HCT from male recipients of female donor grafts. In one of these recipients, a CD8+ T cell response was observed against a peptide stretch encoded by the UTY gene. Another bioinformatics tool, HLArestrictor, was used to identify the optimal peptide and HLA-restriction element. Using peptide/HLA tetramers, the specificity of the CD8+ T cell response was successfully validated as being HLA-A*24:02-restricted and directed against the male UTY(139-147) peptide. Functional analysis of these T cells demonstrated male UTY(139-147) peptide-specific cytokine secretion (IFNγ, TNFα and MIP-1β) and cytotoxic degranulation (CD107a). In contrast, no responses were seen when the T cells were stimulated with patient tumour cells alone. CD8+ T cells specific for this new H-Y-mHag were found in three of five HLA-A*24:02-positive male recipients of female donor HCT grafts available for this study.

KW - Amino Acid Sequence

KW - Blood Cells

KW - CD8-Positive T-Lymphocytes

KW - Epitopes

KW - Female

KW - HLA-A24 Antigen

KW - Humans

KW - Male

KW - Minor Histocompatibility Antigens

KW - Nuclear Proteins

KW - Transplantation, Homologous

U2 - 10.1111/j.1365-3083.2012.02708.x

DO - 10.1111/j.1365-3083.2012.02708.x

M3 - Journal article

C2 - 22536994

SN - 0300-9475

VL - 76

SP - 141

EP - 150

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

IS - 2

ER -