title: HLA-AR, an inactivated antigen-presenting locus related to HLA-A. Implications for the evolution of the MHC.
abstract: The MHC contains many class I genes other than those known to present peptides to T lymphocytes. These additional class I genes vary between species and their functions are unknown. Genes involved in Ag presentation, HLA-A,B,C in humans, are highly diverse whereas other class I genes are of much more limited diversity. We have studied alleles of a gene, HLA-AR, that is closely linked and structurally related to HLA-A; properties consistent with these two loci having been formed by a gene duplication. Compared to HLA-A the diversity in HLA-AR is much less, and does not focus on residues of a putative Ag recognition site. However, the structure of HLA-AR alleles closely resembles those encoding Ag-presenting molecules, although the presence of one or two deleterious mutations prevents these alleles being active in Ag presentation. These results suggest HLA-AR derives from an Ag-presenting locus that became inactivated, possibly as a result of positive natural selection due to changing demands on T cell immunity. Thus absence of diversity may sometimes correlate with loss rather than preservation of function in class I MHC genes.
authors.affiliation: Department of Cell Biology, Stanford University, CA 94305.
authors.forename: J
authors.initials: J
authors.lastname: Zemmour
authors.forename: B H
authors.initials: BH
authors.lastname: Koller
authors.forename: P D
authors.initials: PD
authors.lastname: Ennis
authors.forename: D E
authors.initials: DE
authors.lastname: Geraghty
authors.forename: D A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
authors.forename: P
authors.initials: P
authors.lastname: Parham
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007438:Introns; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D021382:Protein Sorting Signals / Q000276:immunology
chemical_list: C063775:HLA-AR antigen; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals