Conservation of minor histocompatibility antigens between human and non-human primates.
It is well accepted that minor histocompatibility antigens (mHag) can function as transplantation barriers between HLA-matched individuals. Little is known about the molecular nature and evolutionary conservation of mHag. It is only very recently that the first human mHag were identified. The HLA-A2.1-restricted mHag HA-2 and the HLA-B7-restricted mHag H-Y appeared to be peptides derived from polymorphic self proteins. Here we show that the HLA-A2.1-restricted mHag HA-1, HA-2, and the H-Y peptides are conserved between man, chimpanzees and rhesus macaques. Human cytotoxic T cell clones specific for the HLA-A2.1-restricted mHag HA-1, HA-2, and H-Y recognized HLA-A2.1 gene-transfected chimpanzee and rhesus macaque cells. High-pressure liquid chromatography fractionation of HLA-A2.1-bound peptides isolated from the HLA-A2.1-transfected chimpanzee cells revealed that the chimpanzee HA-1 and HA-2 co-eluted with the human HA-1 and HA-2. Subsequent amino acid sequencing showed that the chimpanzee HA-2 peptide is identical to the human HA-2 peptide. Our functional and biochemical results demonstrate that mHag peptides are conserved for over 35 million years.
den Haan
J M
JM
Department of Immunohaematology and Bloodbank, Leiden University Hospital, The Netherlands. haan.j@rulgca.leidenuniv.nl
Bontrop
R E
RE
Pool
J
J
Sherman
N
N
Blokland
E
E
Engelhard
V H
VH
Hunt
D F
DF
Goulmy
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D002999:Clone Cells; D017124:Conserved Sequence / Q000276:immunology; D006182:H-Y Antigen / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology*; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D002679:Pan troglodytes / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000276:immunology
D006182:H-Y Antigen; C080145:HA-2 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins