UTYgene 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

Autor: Vogt, Mario H.J., Goulmy, Els, Kloosterboer, Freke M., Blokland, Els, de Paus, Roel A., Willemze, Roel, Falkenburg, J. H. Frederik
Zdroj: Blood; November 2000, Vol. 96 Issue: 9 p3126-3132, 7p
Abstrakt: 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 SMCYgene. Another CTL clone recognized an HLA-B60–restricted H-Y antigen. In this study UTYwas 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.
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