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.
Martin
P J
PJ
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, USA.
Petersdorf
E W
EW
Anasetti
C
C
Hansen
J A
JA
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014182:Transplantation, Autologous
D006680:HLA Antigens