HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women

Abstract

A crucial requirement in the rational design of a prophylactic vaccine against the human immunodeficiency virus (HIV) is to establish whether or not protective immunity can occur following natural infection. The immune response to HIV infection is characterized by very vigorous HIV-specific cytotoxic T-lymphocyte (CTL) activity. We have identified four HIV-1 and HIV-2 cross-reactive peptide epitopes, presented to CTL from HIV-infected Gambians by HLA-B35 (the most common Gambian class I HLA molecule). These peptides were used to elicit HIV-specific CTLs from three out of six repeatedly exposed but HIV-seronegative female prostitutes with HLA-B35. These women remain seronegative with no evidence of HIV infection by polymerase chain reaction or viral culture. Their CTL activity may represent protective immunity against HIV infection.

Identification of type-specific cytotoxic T lymphocyte responses to homologous viral proteins in laboratory workers accidentally infected with HIV-1.

“…A vigorous virus-specific CTL response is a major component of the host immune response in long-term nonprogressors (5)(6)(7). The observation that CTL activity declines with disease progression (7,8) and the demonstration of HIV-1-specific CTL activity in exposed uninfected individuals further supports a protective role for CTL (9,10). These data, together with similar data from animal models in which antiviral CTL can prevent disease (11) as well as clear established infections (12), suggest that HIV-1-specific CTL are likely to have a protective activity against HIV infection.…”

Production and crystallization of MHC class I B allele single peptide complexes

“…HLA B53, a common African allele, which has been shown to be associated with resistance to severe malaria in the Gambia [20], has been crystallized with two 9-mer peptide epitopes, Is6 (KPIVQYDNF) from the malaria parasite P. falciparum [21] and TPYDINQML from the Gag protein of HIV-2 [22]. The related allele HLA B3501 has also been crystallized complexed with the 8-mer nef peptide (VPLRPMTY) [23] which comes from a region conserved in the HIV-1 and HIV-2 genomes.…”

Frequency of polymorphisms of genes coding for HIV-1 co-receptors CCR5 and CCR2 in a Brazilian population

“…It has been shown that the CD 4 + T-cells of these individuals are highly resistant in vitro to the entry of primary macrophage-tropic virus, but are readily infected with transformed T-cell-line-adapted viruses [11]. Subsequent to this discovery, a 32-base pair deletion (∆32) in the CCR5 gene was identified in some Caucasians [12,13].…”