Broadly immunogenic HLA class I supertype-restricted elite CTL epitopes recognized in a diverse population infected with different HIV-1 subtypes.
The genetic variations of the HIV-1 virus and its human host constitute major obstacles for obtaining potent HIV-1-specific CTL responses in individuals of diverse ethnic backgrounds infected with different HIV-1 variants. In this study, we developed and used a novel algorithm to select 184 predicted epitopes representing seven different HLA class I supertypes that together constitute a broad coverage of the different HIV-1 strains as well as the human HLA alleles. Of the tested 184 HLA class I-restricted epitopes, 114 were recognized by at least one study subject, and 45 were novel epitopes, not previously described in the HIV-1 immunology database. In addition, we identified 21 "elite" epitopes that induced CTL responses in at least 4 of the 31 patients. A majority (27 of 31) of the study population recognized one or more of these highly immunogenic epitopes. We also found a limited set of 9 epitopes that together induced HIV-1-specific CTL responses in all HIV-1-responsive patients in this study. Our results have important implications for the validation of potent CTL responses and show that the goal for a vaccine candidate in inducing broadly reactive CTL immune responses is attainable.
Pérez
Carina L
CL
Department of Microbiology, Cell Biology, and Tumor Biology, Karolinska Institutet, and The Swedish Institute of Infectious Disease Control, Stockholm, Sweden.
Larsen
Mette V
MV
Gustafsson
Rasmus
R
Norström
Melissa M
MM
Atlas
Ann
A
Nixon
Douglas F
DF
Nielsen
Morten
M
Lund
Ole
O
Karlsson
Annika C
AC
D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000145:classification / Q000453:epidemiology / Q000276:immunology*; D015497:HIV-1 / Q000145:classification* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I