ABO glycosyltransferases as potential source of minor histocompatibility antigens in allogeneic peripheral blood progenitor cell transplantation.
BACKGROUND
Most studies indicate that the incidence of graft-versus-host disease (GVHD) is not increased in ABO-mismatched allogeneic peripheral blood progenitor cell transplantation. These studies exclusively looked at ABO phenotypes without considering the fact that different genotypes hide behind identical phenotypes that encode for different sets of glycosyltransferases, thus providing a source for minor histocompatibility antigens (mHags).


METHODS
Therefore, whether peptides derived from ABO glycosyltransferases are capable of stimulating peptide-specific T cells was investigated. T-cell responses were identified by measuring intracellular interleukin-2 expression.


RESULTS
Individuals with ABO genotypes encoding glycosyltransferases lacking the peptide sequences used for stimulation showed T-cell responses, whereas those expressing glycosyltransferases containing the respective peptide sequences proved to be tolerant, indicating that ABO peptides are allogeneic and may act as mHags. Interestingly, even ABO*O individuals were tolerant to O glycosyltransferase-derived peptides, which strongly suggests that truncated O transferases are expressed.


CONCLUSIONS
Considering allelic ABO sequences, at least 15 percent of all phenotypically ABO-matched transplant pairs can be expected to have genotype constellations relevant to GVHD. Therefore, the genotype behind the ABO blood group phenotype should be considered to answer the question of whether ABO mismatch is a risk factor of GVHD.
Eiz-Vesper
Britta
B
Department of Transfusion Medicine, Hannover Medical School, Hannover, Germany.
Seltsam
Axel
A
Blasczyk
Rainer
R
D000017:ABO Blood-Group System / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D001787:Blood Group Incompatibility / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D016695:Glycosyltransferases / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D018448:Models, Immunological; D036102:Peripheral Blood Stem Cell Transplantation; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
D000017:ABO Blood-Group System; D015415:Biomarkers; D007376:Interleukin-2; D015778:Minor Histocompatibility Antigens; D016695:Glycosyltransferases