title: Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins.
abstract: BACKGROUND
  While human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes.
  
  
  RESULTS
  We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants, affirmed that the degree of similarity to the host was significantly lower for peptides with reactive epitopes than for those that were not recognized.
  
  
  CONCLUSIONS
  Our results suggest that antigenic motifs that are scarcely represented in human proteins might represent more immunogenic CTL targets not selected against in the host. This observation could provide guidance in the design of more effective HIV immunogens, as sequences devoid of host-like features might afford superior immune reactivity.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Morgane
authors.initials: M
authors.lastname: Rolland
authors.forename: David C
authors.initials: DC
authors.lastname: Nickle
authors.forename: Wenjie
authors.initials: W
authors.lastname: Deng
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Nebosja
authors.initials: N
authors.lastname: Jojic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jojic
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
mesh_terms: D000595:Amino Acid Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D015693:Gene Products, nef / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011506:Proteins / Q000737:chemistry / Q000276:immunology*; D020543:Proteome; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*