Cytotoxic T Lymphocytes in Humans Exposed to Plasmodium falciparum by Immunization or Natural Exposure

Hoffman, S. L.; Malik, Anita

doi:10.1007/978-3-642-78530-6_11

Cited by 3 publications

(4 citation statements)

References 50 publications

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“…This finding is consistent with the notion that malaria-specific CD8 cells recognize peptide epitopes of liver-stage Ag that are processed and presented by HLA class I-bearing hepatocytes. Since elimination of P. falciparum in hepatocytes may be mediated or augmented by T cells restricted by HLA class I (12,18,29,41,42), it will be important in future studies to ascertain whether the observed CD8 cell IFN-␥, as well as CTL, responses to these peptides differ according to HLA types common in the Wosera area. These experiments are more properly done with 9-mer peptides than the 20-to 30-mer peptides used here, since multiple major histocompatibility complex class I-restricted responses may be elicited by the latter constructs.…”

Section: Discussionmentioning

confidence: 99%

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T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic

et al. 1997

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Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-␥) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 ؋ 10 6 cells, was derived primarily from CD8 ؉ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-␥ response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-␥, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N-and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-␥ responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans.

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Section: Discussionmentioning

confidence: 99%

“…Lymphocyte proliferation responses to polymorphic regions of CSP have been noted among adults living in other areas where malaria is endemic (13,44). CTL produced in response to peptide epitopes of SSP2, CSP, and several other pre-erythrocytic Ag were detectable in children and adults in The Gambia and Tanzania (1,12,18,24,37).…”

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confidence: 99%

T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic

et al. 1997

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“…It is well appreciated that cell-mediated immunity (CMI) plays an important protective role against both HIV and acute malaria infections. 3,4 Because HIV infections result in generalized immunosuppression by depleting CD4 + T lymphocytes, HIV/AIDS can have a broad impact on the ability of the immune system of HIV-infected patients to control opportunistic infections and other infectious diseases. Previous studies have demonstrated that malaria infection is exacerbated in HIV-positive patients.…”

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confidence: 99%

Short Report: Analysis of Anti-Malaria Immune Response During Human Immunodeficiency Virus Infection in Adults in Kinshasa, Democratic Republic of the Congo

Mwandagalirwa

Nzila

Mussey³

et al. 2003

The American Journal of Tropical Medicine and Hygiene

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Co-infection of human immunodeficiency virus and malaria is not uncommon in people living in sub-Saharan Africa. Since HIV infection results in immune deficiency, it may alter the ability of HIV patients to mount proper immune responses against malaria parasites. We measured specific malaria antibodies in 47 specimens from 25 couples from Kinshasa, Democratic Republic of the Congo (DRC), according to their HIV status, and investigated probable interaction between malaria and HIV infection. Plasma samples were analyzed for HIV markers (western blot and viral load) and malaria parasite-specific antibody (antibody titer, pattern of antigen recognized by western blotting, and parasite neutralizing antibodies assayed by growth inhibition). No correlation was identified between measured HIV infection status and malaria-specific parameters.

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“…Overall, while some amino acid substitutions abrogated the IFN-γ induction potential of immunodominant peptides or resulted in positive responses in both allele peptides albeit at different response magnitudes in some subjects, similar substitutions in peptides did not affect response induction in other subjects. Deciphering these has significant implications for the design of subunit T cell epitope-based vaccine expected to work through the induction of potent IFN-γ responses [33,38], since only a careful selection of relevant parasite strain-transcending peptides will ensure broad applicability of such vaccines. It is possible that a clearer observation can be made with analysis involving a much greater number of subjects.…”

Section: Plos Onementioning

confidence: 99%

Comparative analysis of the ex vivo IFN-gamma responses to CD8+ T cell epitopes within allelic forms of PfAMA1 in subjects with natural exposure to malaria

et al. 2021

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Antigen polymorphisms in essential malarial antigens are a key challenge to the design and development of broadly effective malaria vaccines. The effect of polymorphisms on antibody responses is fairly well studied while much fewer studies have assessed this for T cell responses. This study investigated the effect of allelic polymorphisms in the malarial antigen apical membrane antigen 1 (AMA1) on ex vivo T cell-specific IFN-γ responses in subjects with lifelong exposure to malaria. Human leukocyte antigen (HLA) class I-restricted peptides from the 3D7 clone AMA1 were bioinformatically predicted and those with variant amino acid positions used to select corresponding allelic sequences from the 7G8, FVO, FC27 and tm284 parasite strains. A total of 91 AMA1 9-10mer peptides from the five parasite strains were identified, synthesized, grouped into 42 allele sets and used to stimulate PBMCs from seven HLA class 1-typed subjects in IFN-γ ELISpot assays. PBMCs from four of the seven subjects (57%) made positive responses to 18 peptides within 12 allele sets. Fifty percent of the 18 positive peptides were from the 3D7 parasite variant. Amino acid substitutions that were associated with IFN-γ response abrogation were more frequently found at positions 1 and 6 of the tested peptides, but substitutions did not show a clear pattern of association with response abrogation. Thus, while we show some evidence of polymorphisms affecting T cell response induction, other factors including TCR recognition of HLA-peptide complexes may also be at play.

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Cytotoxic T Lymphocytes in Humans Exposed to Plasmodium falciparum by Immunization or Natural Exposure

Cited by 3 publications

References 50 publications

T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic

T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic

Short Report: Analysis of Anti-Malaria Immune Response During Human Immunodeficiency Virus Infection in Adults in Kinshasa, Democratic Republic of the Congo

Comparative analysis of the ex vivo IFN-gamma responses to CD8+ T cell epitopes within allelic forms of PfAMA1 in subjects with natural exposure to malaria

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