UTY gene codes for an HLA-B60-restricted human male-specific minor histocompatibility antigen involved in stem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition.
Rejection of a graft after human leukocyte antigen (HLA)-identical stem cell transplantation (SCT) can be caused by recipient's immunocompetent T lymphocytes recognizing minor histocompatibility antigens on donor stem cells. During rejection of a male stem cell graft by a female recipient, 2 male (H-Y)-specific cytotoxic T lymphocyte (CTL) clones were isolated from peripheral blood. One CTL clone recognized an HLA-A2-restricted H-Y antigen, encoded by the SMCY gene. Another CTL clone recognized an HLA-B60-restricted H-Y antigen. In this study UTY was identified as the gene coding for the HLA-B60-restricted H-Y antigen. The UTY-derived H-Y antigen was characterized as a 10-amino acid residue peptide, RESEEESVSL. Although the epitope differed by 3 amino acids from its X-homologue, UTX, only 2 polymorphisms were essential for recognition by the CTL clone HLA-B60 HY. These results illustrate that CTLs against several H-Y antigens derived from different proteins can contribute simultaneously to graft rejection after HLA-identical, sex-mismatched SCT. Moreover, RESEEESVSL-specific T cells could be isolated from a female HLA-B60+ patient with myelodysplastic syndrome who has been treated with multiple blood transfusions, but not from control healthy HLA-B60+ female donors. This may indicate that RESEEESVSL-reactive T cells are more common in sensitized patients.
Vogt
M H
MH
Departments of Hematology and Immunohematology and Bloodbank, Leiden University Medical Center, Leiden, The Netherlands. m.h.j.vogt@lumc.nl
Goulmy
E
E
Kloosterboer
F M
FM
Blokland
E
E
de Paus
R A
RA
Willemze
R
R
Falkenburg
J H
JH
D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006182:H-Y Antigen / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D006367:HeLa Cells; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011110:Polymorphism, Genetic; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014998:Y Chromosome
D006182:H-Y Antigen; D015235:HLA-B Antigens; C081918:HLA-B60 antigen; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; C484453:UTY protein, human