The 1170 A–P single-nucleotide polymorphism (SNP) in the Her-2/neu protein (HER2) as a minor histocompatibility antigen (mHag)

Wenandy, Lynn; Køllgaard, Tania; Letsch, Anne; Andersen, Rikke; Stather, David R.; Seremet, Tina; Svane, Inge Marie; Vindeløv, L; Andersen, Mads Hald; Straten, Per thor

doi:10.1038/leu.2009.112

Cited by 7 publications

(5 citation statements)

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“…MHC molecules are responsible for the presentation of foreign peptides to immune cells and also are mediators of transplant rejection. Minor histocompatibility antigens are derived from functional proteins and can elicit an immune response due to allelic differences between individuals, typically single‐nucleotide polymorphisms (SNPs), insertions, deletions, or presence of the antigen on the Y‐chromosome (Tables and ) …”

Section: Immunogenicity Of Minor Histocompatibility Antigensmentioning

confidence: 99%

“…The antigenic peptide that arises from HA1 results from a single nucleotide difference between the non‐immunogenic peptide (KECVL R DDLLEA) and the immunogenic peptide (KECVL H DDLLEA) . The immunogenic peptide can be presented in the context of at least four different Class I MHCs, including HLA‐A*0201 (Table ) . As a result of the immunogenic SNP, the binding affinity of the HA1 H peptide to the HLA‐A*0201 peptide binding groove on APCs is increased, thus leading to an immunogenic peptide that can be recognized by HLA‐A*0201 restricted T‐cells.…”

Section: Immunogenicity Of Minor Histocompatibility Antigensmentioning

confidence: 99%

“…These mHAgs arise from SNPs, presence on the Y‐chromosome, deletions, insertions, frameshift mutations, nonsense mutations, and splice variants. mHAgs are encoded on the Y‐chromosome (Table ) and on many autosomes (Table ) . Expression of some mHAgs is restricted to hematopoietic cells or a select group of tissues, whereas other mHAgs are expressed ubiquitously.…”

Section: The Discovery Of Minor Histocompatibility Antigensmentioning

confidence: 99%

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Minor Histocompatibility Antigens and the Maternal Immune Response to the Fetus During Pregnancy

Linscheid

Petroff

2013

American J Rep Immunol

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The tolerance of the semiallogeneic fetus by the maternal immune system is an important area of research for understanding how the maternal and fetal systems interact during pregnancy to ensure a successful outcome. Several lines of research reveal that the maternal immune system can recognize and respond to fetal minor histocompatibility antigens during pregnancy. Reactions to these antigens arise because of allelic differences between the mother and fetus, and have been shown more broadly to play an important role in mediating transplantation outcomes. This review outlines the discovery of minor histocompatibility antigens and their importance in solid organ and hematopoietic stem cell transplantations, maternal T-cell responses to minor histocompatibility antigens during pregnancy, expression of minor histocompatibility antigens in the human placenta, and the potential involvement of minor histocompatibility antigens in the development and manifestation of pregnancy complications.

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Section: Immunogenicity Of Minor Histocompatibility Antigensmentioning

confidence: 99%

Section: Immunogenicity Of Minor Histocompatibility Antigensmentioning

confidence: 99%

Section: The Discovery Of Minor Histocompatibility Antigensmentioning

confidence: 99%

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Minor Histocompatibility Antigens and the Maternal Immune Response to the Fetus During Pregnancy

Linscheid

Petroff

2013

American J Rep Immunol

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“…Datasets, software, and computational power seem to be sufficient to generate candidate minor H antigens . Although three autosomally encoded minor H antigens have been identified by the reverse immunology , the major bottleneck seems to be cellular confirmation of the predicted epitopes. Combining reverse immunology with SNP typing of donor–recipient pairs or by implementing the HLA‐peptidome may increase the success rate of this approach.…”

Section: Minor H Antigen Identificationmentioning

confidence: 99%

Minor histocompatibility antigens: past, present, and future

Spierings

2014

Tissue Antigens

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Minor histocompatibility (H) antigens are key molecules driving allo-immune responses in both graft-versus-host-disease (GvHD) and in graft-versus-leukemia (GvL) reactivity in human leukocyte antigen (HLA)-matched hematopoietic stem-cell transplantation (HSCT). Dissection of the dual function of minor H antigens became evident through their different modes of tissue and cell expression, i.e. hematopoietic system-restricted or broad. Broadly expressed minor H antigens can cause both GvHD and GvL effects, while hematopoietic system-restricted minor H antigens are more prone to induce GvL responses. This phenomenon renders the latter group of minor H antigens as curative tools for HSCT-based immunotherapy of hematological malignancies and disorders, in which minor H antigen-specific responses are enhanced in order to eradicate the malignant cells. This article describes the immunogenetics of minor H antigens and methods that have been developed to identify them. Moreover, it summarizes the clinical relevance of minor H antigens in transplantation, with special regards to allogeneic HSCT and solid-organ transplantation.

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“…This strategy has been highly successful for the identification of several tumor-associated Ags and also contributed to the discovery of mHags. 25,26 Over the past decades, T-cell epitope prediction algorithms based on factors such as HLA binding, proteasomal cleavage and TAP (transporter-associated processing) transport were improved and used to predict polymorphic T-cell epitopes present on hematopoietic-restricted proteins with a favorable mHag phenotype frequency. 5,27 These strategies, however, had limited success, mainly because of the prediction of significant numbers of false-positive and false-negative candidates.…”

Section: Identification Of Mhags By Reverse Immunology Strategymentioning

confidence: 99%

Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives

Oostvogels

Lokhorst

Mutis

2015

Bone Marrow Transplant

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Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusion are effective treatment modalities for various hematological malignancies. Their therapeutic effect, the graft-versus-tumor (GvT) effect, is based mainly on an alloimmune response of donor T cells directed at tumor cells, in which differences in the expression of minor histocompatibility Ags (mHags) on the cells of the patient and donor have a crucial role. However, these differences are also responsible for induction of sometimes detrimental GvHD. As relapse and development of GvHD pose major threats for a large proportion of allotransplanted patients, additional therapeutic strategies are required. To augment the GvT response without increasing the risk of GvHD, specific mHagdirected immunotherapeutic strategies have been developed. Over the past years, much effort has been put into the identification of therapeutically relevant mHags to enable these strategies for a substantial proportion of patients. Currently, the concept of mHag-directed immunotherapy is tested in clinical trials on feasibility, safety and efficacy. In this review, we will summarize the recent developments in mHag identification and the clinical data on mHag-specific immune responses and mHag-directed therapies in patients with hematological malignancies. Finally, we will outline the current challenges and future prospectives in the field.

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The 1170 A–P single-nucleotide polymorphism (SNP) in the Her-2/neu protein (HER2) as a minor histocompatibility antigen (mHag)

Cited by 7 publications

References 7 publications

Minor Histocompatibility Antigens and the Maternal Immune Response to the Fetus During Pregnancy

Minor Histocompatibility Antigens and the Maternal Immune Response to the Fetus During Pregnancy

Minor histocompatibility antigens: past, present, and future

Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives

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