Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses.
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.
Almeida
Coral-Ann M
CA
Centre for Clinical Immunology and Biomedical Statistics, Institute of Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia.
Roberts
Steven G
SG
Laird
Rebecca
R
McKinnon
Elizabeth
E
Ahmad
Imran
I
Keane
Niamh M
NM
Chopra
Abha
A
Kadie
Carl
C
Heckerman
David
D
Mallal
Simon
S
John
Mina
M
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
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D010455:Peptides; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma