Natural t-cell responses against minor histocompatibility antigen (mhag) hy following hla-matched hematopoietic cell transplantation: what are the requirements for a ‘good’ mhag?

Access through your institution Buy or subscribe Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative treatment modality for several hematologic

malignancies. Conventional myeloablative conditioning regimens are associated with high treatment-related mortality. To this end, the introduction of nonmyeloablative (NMA) conditioning

implies that older and more frail patients can be offered HCT, and recent data suggest comparable outcome of conventional and NMA–HCT, both with regards to efficacy and side effects, at

least for selected indications.1 The curative principle in allogeneic HCT with NMA conditioning is solely related to the graft-versus-leukemia (GVL) effect, and several lines of evidence

strongly suggest that donor T cells are the main effectors. In human leukocyte antigen (HLA), identical sibling HCT, T-cell responses to minor histocompatibility antigens (mHags) are—at

least in part—responsible for the GVL effect but also cause graft-versus-host disease (GVHD). GVHD represents a major side effect of HCT, and it is well established that there exists

correspondence between the GVL effect and GVHD. As a consequence, increased knowledge concerning mechanisms at play and the targets recognized may set the stage for development of treatment

strategies that focus on induction of GVL in the absence of GVHD.2 Obviously, increased insight into the cells, molecules and antigens involved with GVL and GVHD are important to possibly be

able to control and direct these events more precisely. mHags are known to represent prominent target structures in the HCT setting.3 In general, mHags may derive from antigens expressed on

the male Y chromosome, or from polymorphic proteins encoded on autosomal chromosomes. A limited number of mHags has been characterized, but the HA-1 and HA-2 antigens—derived from

nucleotide polymorphisms in proteins of hematopoietic lineage—have been shown to represent prominent targets at mismatch and therefore represent ideal target structures that could be used in

a therapeutic setting, for example, vaccination in combination with HCT.4 However, the practical applicability of single nucleotide polymorphism derived mHags in cancer therapy obviously

depends on the frequencies of the individual single nucleotide polymorphism in the population, which for several of the characterized mHags are quite low.3, 5 Moreover, the frequencies of

these mHags display significant differences among populations even in Europe.6 Conversely, Histocompatibility Y (HY)-derived mHags are relevant also in practical terms as this group of

antigens are potentially relevant in all female to male HCT, although it should be mentioned that female to male HCT is preferentially avoided due to a higher risk of GVHD. Concerning Y

chromosome encoded mHags, the Y-chromosomal protein SMCY-derived mHag restricted by HLA-A2.01; FIDSYICQV (HY-A2)7 could represent an important target as data from other studies suggested the

dominance of this antigen at parity for HA-1/2 antigens.8, 9, 10 This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

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antigens. _Front Biosci_ 2007; 12: 3302–3311. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank Tina Seremet for excellent technical assistance. We also

thank Jørgen Schøller, DAKO for supply of HY/dextramer complexes. The study was supported by the Danish Cancer Society, the Novo Nordisk Foundation, Danish Medical Research Council and the

Danish Foundation for Cancer Research. Eric Spierings was a special fellow of the Leukemia Society of America (3314-05). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of

Hematology, Center for Cancer Immune Therapy (CCIT), University Hospital Herlev, Herlev Ringvej 75, Herlev, Denmark T Kollgaard, S Reker Hadrup, M H Andersen & P thor Straten *

Department of Hematology, The Allo-HCT Laboratory, Rigshospitalet, Copenhagen, Denmark S L Petersen, T N Masmas & L Vindeløv * Department of Immunohematology and Blood Transfusion,

Leiden University Medical Center, Leiden, The Netherlands E Spierings Authors * T Kollgaard View author publications You can also search for this author inPubMed Google Scholar * S Reker

Hadrup View author publications You can also search for this author inPubMed Google Scholar * S L Petersen View author publications You can also search for this author inPubMed Google

Scholar * T N Masmas View author publications You can also search for this author inPubMed Google Scholar * M H Andersen View author publications You can also search for this author inPubMed

 Google Scholar * E Spierings View author publications You can also search for this author inPubMed Google Scholar * L Vindeløv View author publications You can also search for this author

inPubMed Google Scholar * P thor Straten View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to P thor Straten. RIGHTS

AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kollgaard, T., Hadrup, S., Petersen, S. _et al._ Natural T-cell responses against minor histocompatibility

antigen (mHag) HY following HLA-matched hematopoietic cell transplantation: what are the requirements for a ‘good’ mHag?. _Leukemia_ 22, 1948–1951 (2008). https://doi.org/10.1038/leu.2008.75

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