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HLA homozygosity and the risk of graft-versus-host disease
P J Martin1, E W Petersdorf, C Anasetti
1Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, USA.
We explored the relationship between HLA homozygosity and risk of graft-versus-host disease (GVHD) after allogeneic marrow transplantation from an HLA-genotypically identical sibling. If the variety of minor histocompatibility antigens is decreased by the restricted diversity of major histocompatibility complex (MHC) molecules capable of presenting allogeneic peptides in HLA-homozygous individuals, then the risk of GVHD should be decreased in comparison to HLA-heterozygous marrow transplant recipients. Contrary to expectations, we found that HLA-homozygous individuals and HLA-heterozygous individuals have comparable risks of GVHD. We propose that the unexpectedly high incidence of GVHD in HLA-homozygous individuals can be explained by determinant density effects that enable certain peptide-MHC complexes to function as minor antigens on HLA-homozygous antigen-presenting cells but not on HLA-heterozygous antigen-presenting cells. Thus the variety of minor antigens expressed by the two types of cells might be similar, despite the differences in the diversity of HLA molecules.
We explored the relationship between HLA homozygosity and risk of graft-versus-host disease (GVHD) after allogeneic marrow transplantation from an HLA-genotypically identical sibling. If the variety of minor histocompatibility antigens is decreased by the restricted diversity of major histocompatibility complex (MHC) molecules capable of presenting allogeneic peptides in HLA-homozygous individuals, then the risk of GVHD should be decreased in comparison to HLA-heterozygous marrow transplant recipients. Contrary to expectations, we found that HLA-homozygous individuals and HLA-heterozygous individuals have comparable risks of GVHD. We propose that the unexpectedly high incidence of GVHD in HLA-homozygous individuals can be explained by determinant density effects that enable certain peptide-MHC complexes to function as minor antigens on HLA-homozygous antigen-presenting cells but not on HLA-heterozygous antigen-presenting cells. Thus the variety of minor antigens expressed by the two types of cells might be similar, despite the differences in the diversity of HLA molecules.