title: HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1.
abstract: BACKGROUND
  Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression.
  
  
  RESULTS
  In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8(+) T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8(+) T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8(+) T cell response during primary infection.
  
  
  CONCLUSIONS
  These data demonstrate consistent immunodominance patterns of HIV-1-specific CD8(+) T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Kalife
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Mary N
authors.initials: MN
authors.lastname: Johnston
authors.forename: Nicole
authors.initials: N
authors.lastname: Burgett
authors.forename: Martha E
authors.initials: ME
authors.lastname: Swartz
authors.forename: Amy
authors.initials: A
authors.lastname: Yang
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Angela
authors.initials: A
authors.lastname: Meier
authors.forename: Juergen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Heiko
authors.initials: H
authors.lastname: Jessen
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology*; D000483:Alleles; D000940:Antigenic Variation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008297:Male; D016016:Proportional Hazards Models
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D016056:Immunodominant Epitopes