title: Evolutionary conservation of major histocompatibility complex-DR/peptide/T cell interactions in primates.
abstract: Many major histocompatibility complex (MHC) polymorphisms originate from ancient structures that predate speciation. As a consequence, members of the Mhc-DRB1*03 allelic lineage are not only present in humans but in chimpanzees and rhesus macaques as well. This emphasizes that Mhc-DRB1*03 members must have been present in a common ancestor of these primate species that lived about 30 million years ago. Due to the accumulation of genetic variation, however, alleles of the Mhc-DRB1*03 lineage exhibit species-unique sequences. To investigate the biological importance of such conservation and variation, we have studied both the binding and antigen presentation capacity of various trans-species Mhc-DRB1*03 lineage members. Here we show that p3-13 of the 65-kD heat-shock protein (hsp65) of Mycobacterium leprae and M. tuberculosis binds not only to HLA-DR17(3) but also to some chimpanzee and rhesus macaque class II-positive cells. Comparison of the corresponding human, chimpanzee, and rhesus macaque Mhc-DRB1*03 lineage members revealed the presence of uniquely shared amino acid residues, at positions 9-13 and 26-31, of the antigen-binding site that are critical for p3-13 binding. In addition it is shown that several nonhuman primate antigen-presenting cells that bind p3-13 can activate HLA-DR17-restricted T cells. Certain amino acid replacements, however, in Mhc-DRB1*03 lineage members did not influence peptide binding or T cell recognition. Therefore, these studies demonstrate that some polymorphic amino acid residues (motifs) within the antigen-binding site of MHC class II molecules that are crucial for peptide binding and recognition by the T cell receptor have been conserved for over 30 million years.
authors.affiliation: Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Geluk
authors.forename: D G
authors.initials: DG
authors.lastname: Elferink
authors.forename: B L
authors.initials: BL
authors.lastname: Slierendregt
authors.forename: K E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: R R
authors.initials: RR
authors.lastname: de Vries
authors.forename: T H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: R E
authors.initials: RE
authors.lastname: Bontrop
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism; D001667:Binding, Competitive; D005075:Biological Evolution; D002460:Cell Line; D006684:HLA-DR Antigens / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006360:Heat-Shock Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D002679:Pan troglodytes; D010446:Peptide Fragments / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments