Failure to detect MHC class II associations of the human immune response induced by repeated malaria infections to the Plasmodium falciparum antigen Pf155/RESA

Abstract

Available evidence suggests that human T and B cell responses to a major Plasmodium falciparum malaria antigen (Pf155/RESA) in individuals primed by repeated infections are genetically regulated. In the present study we have attempted to establish whether these regulations reflect genetic restrictions imposed on the immune response by class II molecules of the donor's MHC system. T cell activation (proliferation and IFN-gamma release in vitro) and antibody activity (ELISA) were assayed with synthetic peptides corresponding to major Pf155/RESA epitopes. To associate T cell and antibody responses with the donors' MHC class II genotypes, leukocytes from 145 donors living in holo- or hyperendemic regions of Africa (Liberia, Gambia, Madagascar) were used for genomic HLA class II typing of their DRB-DQA and DQB genes by means of restriction fragment length analysis (RFLP). No associations between T cell responses and HLA-DR or -DQ alleles or DRB-DQA-DQB haplotypes were seen among the West Africans even when the donors were divided into high, medium or low responders. This was also true for a small group of HLA class II identical Malagasy donors including three pairs of twins. However, while the T cell responses between the twin pairs varied, those within the pairs were similar. Very similar findings were made with antibodies binding to Pf155/RESA peptides. Our data imply that the impact of MHC class II gene products on specific immune responses to Pf155/RESA epitopes is weak and hard to demonstrate in outbred human populations naturally primed by infection. This may be due to genetic regulations by other, non-HLA class II coded factors superimposed on possible HLA class II restrictions.

Human immune responses to the highly repetitive Plasmodium falciparum antigen Pf332.

“…However, there was no evidence for an association between human major histocompatibility complex (MHC) class II haplotypes and responsiveness to certain epitopes, which is consistent with what has been observed with other asexual blood-stage antigens of the P. falciparum malaria parasite. [47][48][49][50] This is not surprising in view of the fact that humans are highly polymorphic at the MHC class II loci whereas inbred mice express a very limited set of H-2 class II molecules. Still, some resemblance between the analyses of T cell responses to EB200 in mice and humans was seen.…”

IgE elevation and IgE anti-malarial antibodies in Plasmodium falciparum malaria; association of high IgE levels with cerebral malaria

“…The children were not matched for area of residence or ethnic group, but the patients in the two hospitals were recruited from overlapping areas and their ethnic composition was similar, reflecting the proportion of the various groups in the areas [15]. Blood was also obtained from 54 residents (aged 2-35 years) of three villages in the central highlands of Madagascar [12,16] where F. falciparum malaria had recently (1986) reappeared and is currently hyperendemic [17]. Blood was taken at the beginning of the transmission season.…”

Analysis of the T‐Cell Receptor Vβ Usage in Monozygotic and Dizygotic Twins Living in a Plasmodium falciparum Endemic Area in West Africa

“…Studies of possible HLA associations with a variety of immune responses to malaria antigens have failed to show definitive associations, although some weak associations have been described [4]. By comparing concordances of immune responses to malaria antigens in HLA-typed monozygous (Mz) twins as well as dizygous (Dz) twins the results revealed that non-MHC genes are a major determinant of proliferative T cell responses and also contribute to antibody responses [5][6][7].…”