Control of Human Immunodeficiency Virus Type 1 Is Associated with HLA-B*13 and Targeting of Multiple Gag-Specific CD8⁺T-Cell Epitopes

Abstract

To better understand relationships between CD8؉ T-cell specificity and the immune control of human immunodeficiency virus type 1 (HIV-1), we analyzed the role of HLA-B*13, an allele associated with low viremia, in a cohort of 578 C clade-infected individuals in Durban, South Africa. Six novel B*13-restricted cytotoxic T lymphocyte epitopes were defined from analyses of 37 B*13-positive subjects, including three Gag epitopes. These B*13-restricted epitopes contribute to a broad Gag-specific CD8 ؉ response that is associated with the control of viremia. These data are consistent with data from studies of other HLA-class I alleles associated with HIV control that have shown that the targeting of multiple Gag epitopes is associated with relative suppression of viremia.

DNA Prime-Boost Vaccine Regimen To Increase Breadth, Magnitude, and Cytotoxicity of the Cellular Immune Responses to Subdominant Gag Epitopes of Simian Immunodeficiency Virus and HIV

“…Gag protein was chosen because CTL responses to Gag, particularly to its proteolytic processing product p24 Gag , have been associated with better control of HIV viremia (19,23,(26)(27)(28)(29)(30)(31). Similarly, a direct correlation between Gag-specific T cell responses prior to infection and control of acute viremia was found in DNA-vaccinated macaques (32).…”

Major histocompatibility complex and its importance towards controlling infection

“…74 Furthermore, HLA-B*13:02 75,76 and B*58:01, 77-79 have also been described as favourable prognostic factors. The HLA-B*44 and HLA-B*57 have been described as favourable factors in both the acute and chronic phases of Sub Saharan Africans seroconverters regarding the association of HLA Class I alleles and protection against HIV infection.…”

Optimizing HIV‐1‐specific CD8+ T‐cell induction by recombinant BCG in prime‐boost regimens with heterologous viral vectors

“…In some vaccination regimens, HIVA afforded protection against model surrogate virus challenges including chimeric EcoHIV/NDK [16]. In humans, broad CD8 1 T-cell responses recognizing multiple epitopes in HIV-1 Gag were associated with a good control of chronic HIV-1 replication [17][18][19]. Thus, the rationale for using a Gag-based immunogen for induction of protective T-cell immunity remains valid, although improved second-generation immunogens that better address the viral diversity and escape are now under evaluation [20,21].…”

“…[17][18][19]. Thus, the rationale for using a Gag-based immunogen for induction of protective T-cell immunity remains valid, although improved second-generation immunogens that better address the viral diversity and escape are now under evaluation [20,21].…”