Major histocompatibility complex class II-restricted antigen presentation across a species barrier: conservation of restriction determinants in evolution.
The existence of at least three alleles of the HLA-DRB3 gene within the human population is evident. These alleles express DRw52 determinants and react with monoclonal antibody (mAb) 7.3.19.1. The polymorphic epitope recognized by 7.3.19.1 is not only present on human cells but is also expressed on chimpanzee (Pan troglodytes) class II-positive cells. The 7.3.19.1 determinant already existed before speciation of man and chimpanzee, and is at least 5,000,000 yr old. Two-dimensional gel electrophoresis demonstrated that the various HLA- and Patr-DRw52 molecules that are reactive with 7.3.19.1 exhibit isoelectric point differences due to primary amino acid heterogeneity, as was confirmed by sequencing data. Sequence comparison allowed us to map the binding site of mAb 7.3.19.1 to the alpha helix of the major histocompatibility complex (MHC) class II DRB1 domain surrounding the antigen-binding cleft. Despite MHC sequence variation, chimpanzee antigen-presenting cells can present antigen (purified protein derivative) to human T cell lines and vice versa. Only the HLA- and Patr-DRw52 molecules were shown to function as restriction elements for antigen presentation across this species barrier. It is concluded that these particular restriction determinants probably have been conserved in evolution. The HLA- and Patr-DRw52 molecules represent alleles displaying polymorphism that has been selected for in evolution. Such "biomutants" may thus be more useful to study the biological significance of MHC molecules than MHC variants that have been generated by in vitro mutagenesis experiments.
Instituut voor Toegepaste Radiobiologie en Immunologie TNO, Primate Center, Rijswijk, The Netherlands.
R E
RE
Bontrop
D G
DG
Elferink
N
N
Otting
M
M
Jonker
R R
RR
de Vries
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology*; D005075:Biological Evolution; D002455:Cell Division; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D007526:Isoelectric Point; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C051104:HLA-DR52 antigen