Molecular analysis of the association of HLA-B53 and resistance to severe malaria

Abstract

The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.

Importance of CD8 T cell-mediated immune response during intracellular parasitic infections and its implications for the development of effective vaccines

“…During natural infection in humans, CD8 T cells specific for epitopes present within different plasmodial antigens have been detected in many individuals with previous contact with P. falciparum (Hill et al 1992, Aidoo et al 1995, Plebanski et al 1997, Gonzalez et al 2000. Because these individuals do not develop sterile immunity against reinfection, these CD8 T cells do not seem to provide a degree of protective immunity similar to the one observed in individuals vaccinated with radiationattenuated sporozoites of P. falciparum.…”

“…In addition to CD8 epitopes recognized by T cells from individuals vaccinated with radiationattenuated sporozoites, other epitopes were determined using cells collected from individuals naturally exposed to malaria (Hill et al 1992, Aidoo et al 1995, Plebanski et al 1997. A list of the CD8 epitopes described in the distinct liver stage antigens of P. falciparum is depicted in Table II.…”

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

“…The first peptide (as 8-mer or 9-mer) causes a cytotoxic T lymphocyte (CTL) response whereas the presence of the variant peptides presented by B8 antagonises this same CTL response [19]. 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.…”

Synthetic peptides based on Chlamydia trachomatis antigens identify cytotoxic T lymphocyte responses in subjects from a trachoma-endemic population

“…HLA-B8-predicted binding peptides conformed to K/R at positions 3 and 5 and L/I at positions 8 or 9. HLA-B35-predicted binding peptides based on C. trachomatis sequences conformed to the motif described by Hill et al [23]. Only sequences with P at position 2 and I, L, M, or Y at positions 8 or 9 were synthesized.…”