title: Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses.
abstract: Since HLA-restricted cytotoxic T-cell responses select specific polymorphisms in HIV-1 sequences and HLA diversity is relatively static in human populations, we investigated the use of peptide epitopes based on sites of HLA-associated adaptation in HIV-1 sequences to stimulate and detect T-cell responses ex vivo. These "HLA-optimised" peptides captured more HIV-1 Nef-specific responses compared with overlapping peptides of a single consensus sequence, in interferon-gamma enzyme linked immunospot assays. Sites of immune selection can reveal more immunogenic epitopes in HLA-diverse populations and offer insights into the nature of HLA-epitope targeting, which could be applied in vaccine design.
authors.affiliation: Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia.
authors.forename: Coral-Ann M
authors.initials: CA
authors.lastname: Almeida
authors.forename: Steven G
authors.initials: SG
authors.lastname: Roberts
authors.forename: Rebecca
authors.initials: R
authors.lastname: Laird
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McKinnon
authors.forename: Imran
authors.initials: I
authors.lastname: Ahmad
authors.forename: Niamh M
authors.initials: NM
authors.lastname: Keane
authors.forename: Abha
authors.initials: A
authors.lastname: Chopra
authors.forename: Carl
authors.initials: C
authors.lastname: Kadie
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Mina
authors.initials: M
authors.lastname: John
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016384:Consensus Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D010455:Peptides / Q000276:immunology; D011110:Polymorphism, Genetic; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D010455:Peptides; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma