HLA homozygosity and the risk of graft‐versus‐host disease

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.