Transplantation Immunology
Minor Histocompatibility antigens
Research interest
Transplantation of organs, tissues, and stem cells frequently leads to immune responses due to histo-incompatibility between donor and recipient. Clinically, these incompatibilities can result in graft rejection or, in the case of stem-cell transplantation, to graft-versus-host reactivity. To avoid these detrimental phenomena, transplantations are ideally performed between Major Histocompatibility Antigen (MHC; HLA in humans)-identical individuals. Nevertheless,
in these cases, similar immune responses can be observed due to incompatibility in minor histocompatibility antigens between the HLA-matched donor and the recipient. These well-defined incompatibilities are caused by minor histocompatibility antigen-specific donor T cells.
Minor histocompatibility antigens are peptides derived from polymorphic self proteins that can differ between individuals due to genetic polymorphisms. Minor histocompatibility peptides are presented by the various MHC class I and class II molecules. The MHC/minor histocompatibility peptides complexes not only function as transplantation barriers in allogeneic HLA-matched hematopoietic stem-cell and in solid-organ transplantation but also induce immune responses in pregnancy.
Our research is focused on the role of minor histocompatibility antigens in the clinical outcome of organ and stem-cell transplantation in clinical/epidemiological studies. We aim at identifying the genetic polymorphism that underlie these immunogenic disparities between donor and recipient, and investigate their role in graft-versus-host disease.
- Kirsten Thus, PhD student
- Nathalie Bus, Technician
Steric hindrance and fast dissociation explain the lack of immunogenicity of the minor Histocompatibility HA-1Arg null allele.
Spierings E, Gras S, Reiser JB, Mommaas B, Almekinders M, Kester M, Chouquet A, Le Gorrec M, Drijfhout JW, Ossendorp F, Housset D, Goulmy E.
J. Immunol. 2009; 182(8):4809-16.
Phenotype frequencies of autosomal minor Histocompatibility antigens display significant differences among populations.
Spierings E, et. al.
PLoS Genet. 2007; 3(6): e103.
Minor histocompatibility antigens big in tumour therapy.
Spierings E, Wieles B, Goulmy E.
Trends in Immunology 2004;25(2):56-60
Identification of HLA class II-restricted H-Y-specific T-helper epitope evoking CD4+ T-helper cells in H-Y-mismatched transplantation.
Spierings E, Vermeulen CJ, Vogt MH, Doerner LEE, Falkenburg JHF, Mutis T et al.
Lancet 2003;362(9384):610-5.
The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein. Spierings E, Brickner AG, Caldwell JA, Zegveld S, Tatsis N, Blokland E et al.
Blood 2003;102(2):621-9.
2007-2012
National Institute of Health: Hematopoietic Lineage-restricted Minor Histocompatibility Antigens as GVL Targets
2009-2012
Deutsche Forschungsgemeinschaft: FANCY trial – Functional antigen matching in corneal transplantation