title: Advantage of rare HLA supertype in HIV disease progression.
abstract: The highly polymorphic human leukocyte antigen (HLA) class I molecules help to determine the specificity and repertoire of the immune response. The great diversity of these antigen-binding molecules confers differential advantages in responding to pathogens, but presents a major obstacle to distinguishing HLA allele-specific effects. HLA class I supertypes provide a functional classification for the many different HLA alleles that overlap in their peptide-binding specificities. We analyzed the association of these discrete HLA supertypes with HIV disease progression rates in a population of HIV-infected men. We found that HLA supertypes alone and in combination conferred a strong differential advantage in responding to HIV infection, independent of the contribution of single HLA alleles that associate with progression of the disease. The correlation of the frequency of the HLA supertypes with viral load suggests that HIV adapts to the most frequent alleles in the population, providing a selective advantage for those individuals who express rare alleles.
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way Oakland, California 94609, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
authors.forename: Cristina
authors.initials: C
authors.lastname: Sollars
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.forename: Peter T
authors.initials: PT
authors.lastname: Hraber
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hayes
authors.forename: Robert
authors.initials: R
authors.lastname: Funkhouser
authors.forename: Michael
authors.initials: M
authors.lastname: Fugate
authors.forename: James
authors.initials: J
authors.lastname: Theiler
authors.forename: Yen S
authors.initials: YS
authors.lastname: Hsu
authors.forename: Kevin
authors.initials: K
authors.lastname: Kunstman
authors.forename: Samuel
authors.initials: S
authors.lastname: Wu
authors.forename: John
authors.initials: J
authors.lastname: Phair
authors.forename: Henry
authors.initials: H
authors.lastname: Erlich
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
mesh_terms: D020816:Amino Acid Motifs; D001769:Blood / Q000821:virology; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D006680:HLA Antigens; D012367:RNA, Viral; D014764:Viral Proteins