Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 20 February 1998:
Vol. 279. no. 5354, pp. 1173 - 1177
DOI: 10.1126/science.279.5354.1173
Prev | Table of Contents | Next

Research Articles

Association of Malaria Parasite Population Structure, HLA, and Immunological Antagonism

Sarah C. Gilbert, * Magdalena Plebanski, * Sunetra Gupta, Joanne Morris, Martin Cox, Michael Aidoo, Dominic Kwiatkowski, Brian M. Greenwood, Hilton C. Whittle, Adrian V. S. Hill dagger

Host-parasite coevolution has been likened to a molecular arms race, with particular parasite genes evolving to evade specific host defenses. Study of the variants of an antigenic epitope of Plasmodium falciparum that induces a cytotoxic T cell response supports this view. In African children with malaria, the variants present are influenced by the presence of a human leukocyte antigen (HLA) type that restricts the immune response to this epitope. The distribution of parasite variants may be further influenced by the ability of cohabiting parasite strains to facilitate each other's survival by down-regulating cellular immune responses, using altered peptide ligand antagonism.

S. C. Gilbert and M. Cox are at Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Windmill Road, Oxford OX3 7BN, UK. M. Plebanski and M. Aidoo are at Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. S. Gupta is at Wellcome Trust Centre for the Epidemiology of Infectious Diseases, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. J. Morris is at Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. D. Kwiatkowski, B. M. Greenwood, and H. C. Whittle are at Medical Research Council Laboratories, Fajara, Post Office Box 273, The Gambia. A. V. S. Hill is at Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Windmill Road, Oxford OX3 7BN, UK, and Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
*   These authors contributed equally to this research article.

dagger    To whom correspondence should be addressed. E-mail: adrian.hill{at}imm.ox.ac.uk

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Exploring the Molecular Landscape of Host-Parasite Coevolution.
D.E. Allen and T.J. Little (2009)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
A Cluster of Four Surface Antigen Genes Specifically Expressed in Bradyzoites, SAG2CDXY, Plays an Important Role in Toxoplasma gondii Persistence.
J. P. J. Saeij, G. Arrizabalaga, and J. C. Boothroyd (2008)
Infect. Immun. 76, 2402-2410
   Abstract »    Full Text »    PDF »
Plasmodium falciparum Genetic Diversity in Western Kenya Highlands.
D. Zhong, Y. Afrane, A. Githeko, Z. Yang, L. Cui, D. M. Menge, E. A. Temu, and G. Yan (2007)
Am J Trop Med Hyg 77, 1043-1050
   Abstract »    Full Text »    PDF »
Significance of Variation Within HIV, EBV, and KSHV Subtypes.
J. Stebbing, T. Powles, M. Nelson, and M. Bower (2006)
J Int Assoc Physicians AIDS Care (Chic Ill) 5, 93-102
   Abstract »    PDF »
Sequence Variation in the T-Cell Epitopes of the Plasmodium falciparum Circumsporozoite Protein among Field Isolates Is Temporally Stable: a 5-Year Longitudinal Study in Southern Vietnam.
A. Jalloh, H. van Thien, M. U. Ferreira, J. Ohashi, H. Matsuoka, T. Kanbe, A. Kikuchi, and F. Kawamoto (2006)
J. Clin. Microbiol. 44, 1229-1235
   Abstract »    Full Text »    PDF »
The effect of host heterogeneity and parasite intragenomic interactions on parasite population structure.
R. Hamilton, M. Boots, and S. Paterson (2005)
Proc R Soc B 272, 1647-1653
   Abstract »    Full Text »    PDF »
Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis.
C. Scotta, L. Tuosto, A. M. Masci, L. Racioppi, E. Piccolella, and L. Frasca (2005)
J. Leukoc. Biol. 78, 372-382
   Abstract »    Full Text »    PDF »
The Course of Malaria in Mice: Major Histocompatibility Complex (MHC) Effects, but No General MHC Heterozygote Advantage in Single-Strain Infections.
C. Wedekind, M. Walker, and T. J. Little (2005)
Genetics 170, 1427-1430
   Abstract »    Full Text »    PDF »
In Vivo Modulation of T Cell Responses and Protective Immunity by TCR Antagonism during Infection.
L. L. Lau, J. Jiang, and H. Shen (2005)
J. Immunol. 174, 7970-7976
   Abstract »    Full Text »    PDF »
Inverse Associations of Human Leukocyte Antigen and Malaria Parasite Types in Two West African Populations.
K. Young, A. Frodsham, O. K. Doumbo, S. Gupta, A. Dolo, J. T. Hu, K. J. H. Robson, A. Crisanti, A. V. S. Hill, and S. C. Gilbert (2005)
Infect. Immun. 73, 953-955
   Abstract »    Full Text »    PDF »
Antigenic Diversity and Immune Evasion by Malaria Parasites.
M. U. Ferreira, M. da Silva Nunes, and G. Wunderlich (2004)
Clin. Vaccine Immunol. 11, 987-995
   Full Text »    PDF »
Genetics of infectious diseases.
A. J. Frodsham and A. V.S. Hill (2004)
Hum. Mol. Genet. 13, R187-R194
   Abstract »    Full Text »    PDF »
Identification of a Polyclonal B-Cell Activator in Plasmodium falciparum.
D. Donati, L. P. Zhang, Q. Chen, A. Chene, K. Flick, M. Nystrom, M. Wahlgren, and M. T. Bejarano (2004)
Infect. Immun. 72, 5412-5418
   Abstract »    Full Text »    PDF »
Inhibition of T Cell Function During Malaria: Implications for Immunology and Vaccinology.
B. C. Urban and D. J. Roberts (2003)
J. Exp. Med. 197, 137-141
   Full Text »    PDF »
Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells.
C. Ocana-Morgner, M. M. Mota, and A. Rodriguez (2003)
J. Exp. Med. 197, 143-151
   Abstract »    Full Text »    PDF »
Short-term antigen presentation and single clonal burst limit the magnitude of the CD8+ T cell responses to malaria liver stages.
J. C. R. Hafalla, G.-i. Sano, L. H. Carvalho, A. Morrot, and F. Zavala (2002)
PNAS 99, 11819-11824
   Abstract »    Full Text »    PDF »
Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain.
S. Bagot, S. Campino, C. Penha-Goncalves, S. Pied, P.-A. Cazenave, and D. Holmberg (2002)
PNAS 99, 9919-9923
   Abstract »    Full Text »    PDF »
In Vitro Correlates of Ld-Restricted Resistance to Toxoplasmic Encephalitis and Their Critical Dependence on Parasite Strain.
J. J. Johnson, C. W. Roberts, C. Pope, F. Roberts, M. J. Kirisits, R. Estes, E. Mui, T. Krieger, C. R. Brown, J. Forman, et al. (2002)
J. Immunol. 169, 966-973
   Abstract »    Full Text »    PDF »
Susceptibility to Experimental Cerebral Malaria Induced by Plasmodium berghei ANKA in Inbred Mouse Strains Recently Derived from Wild Stock.
S. Bagot, M. Idrissa Boubou, S. Campino, C. Behrschmidt, O. Gorgette, J.-L. Guenet, C. Penha-Goncalves, D. Mazier, S. Pied, and P.-A. Cazenave (2002)
Infect. Immun. 70, 2049-2056
   Abstract »    Full Text »    PDF »
General T-cell receptor antagonists to immunomodulate HLA-A2-restricted minor histocompatibility antigen HA-1-specific T-cell responses.
J. M. M. den Haan, T. Mutis, E. Blokland, A. P. IJzerman, and E. Goulmy (2002)
Blood 99, 985-992
   Abstract »    Full Text »    PDF »
Recombination in the ompA Gene but Not the omcB Gene of Chlamydia Contributes to Serovar-Specific Differences in Tissue Tropism, Immune Surveillance, and Persistence of the Organism.
K. L. Millman, S. Tavare, and D. Dean (2001)
J. Bacteriol. 183, 5997-6008
   Abstract »    Full Text »    PDF »
Gastric Cancer and Human Leukocyte Antigen: Distinct DQ and DR Alleles Are Associated with Development of Gastric Cancer and Infection by Helicobacter pylori.
P. K. E. Magnusson, H. Enroth, I. Eriksson, M. Held, O. Nyrén, L. Engstrand, L.-E. Hansson, and U. B. Gyllensten (2001)
Cancer Res. 61, 2684-2689
   Abstract »    Full Text »
Major Hematologic Diseases in the Developing World-- New Aspects of Diagnosis and Management of Thalassemia, Malarial Anemia, and Acute Leukemia.
P. L. Greenberg, V. Gordeuk, S. Issaragrisil, N. Siritanaratkul, S. Fucharoen, and R. C. Ribeiro (2001)
Hematology 2001, 479-498
   Abstract »    Full Text »    PDF »
Antagonism of Direct Alloreactivity of an HLA-B27-Specific CTL Clone by Altered Peptide Ligands of Its Natural Epitope.
M. Garcia-Peydro, A. Paradela, J. P. Albar, and J. A. L. d. Castro (2000)
J. Immunol. 165, 5680-5685
   Abstract »    Full Text »    PDF »
The HLA System- Second of Two Parts.
J. Klein and A. Sato (2000)
N. Engl. J. Med. 343, 782-786
   Full Text »    PDF »
Detecting low penetrance genes in cancer: the way ahead.
R S Houlston and I P M Tomlinson (2000)
J. Med. Genet. 37, 161-167
   Abstract »    Full Text »
The Cytotoxic T-Lymphocyte Epitope of the Plasmodium falciparum Circumsporozoite Protein Also Modulates the Efficiency of Receptor-Ligand Interaction with Hepatocytes.
D. Rathore and T. F. McCutchan (2000)
Infect. Immun. 68, 740-743
   Abstract »    Full Text »    PDF »
Hypervariable Region 1 Variants Act as TCR Antagonists for Hepatitis C Virus-Specific CD4+ T Cells.
L. Frasca, P. Del Porto, L. Tuosto, B. Marinari, C. Scotta, M. Carbonari, A. Nicosia, and E. Piccolella (1999)
J. Immunol. 163, 650-658
   Abstract »    Full Text »    PDF »
The Surface Protein Superfamily of Trypanosoma cruzi Stimulates a Polarized Th1 Response That Becomes Anergic.
A. E. Millar, M. Wleklinski-Lee, and S. J. Kahn (1999)
J. Immunol. 162, 6092-6099
   Abstract »    Full Text »    PDF »
Cutting Edge: A Test of the Dominant Negative Signal Model for TCR Antagonism.
M. A. Daniels, S. L. Schober, K. A. Hogquist, and S. C. Jameson (1999)
J. Immunol. 162, 3761-3764
   Abstract »    Full Text »    PDF »
HLA and HIV-1: Heterozygote Advantage and B*35-Cw*04 Disadvantage.
M. Carrington, G. W. Nelson, M. P. Martin, T. Kissner, D. Vlahov, J. J. Goedert, R. Kaslow, S. Buchbinder, K. Hoots, and S. J. O'Brien (1999)
Science 283, 1748-1752
   Abstract »    Full Text »
The effect of antibody-dependent enhancement on the transmission dynamics and persistence of multiple-strain pathogens.
N. Ferguson, R. Anderson, and S. Gupta (1999)
PNAS 96, 790-794
   Abstract »    Full Text »    PDF »
Discrete-Event Models of Mixed-Phenotype Plasmodium falciparum Malaria..
F. E. McKenzie, R. C. Wong, and W. H. Bossert (1999)
SIMULATION 73, 213-217
   Abstract »    PDF »
T cell receptor antagonism in vivo, at last.
S. C. Jameson (1998)
PNAS 95, 14001-14002
   Full Text »    PDF »
In vivo antagonism of a T cell response by an endogenously expressed ligand.
D. Basu, C. B. Williams, and P. M. Allen (1998)
PNAS 95, 14332-14336
   Abstract »    Full Text »    PDF »
The p29 and p35 Immunodominant Antigens of Neospora caninum Tachyzoites Are Homologous to the Family of Surface Antigens of Toxoplasma gondii.
D. K. Howe, A. C. Crawford, D. Lindsay, and L. D. Sibley (1998)
Infect. Immun. 66, 5322-5328
   Abstract »    Full Text »    PDF »
The Surface of Toxoplasma Tachyzoites Is Dominated by a Family of Glycosylphosphatidylinositol-Anchored Antigens Related to SAG1.
I. D. Manger, A. B. Hehl, and J. C. Boothroyd (1998)
Infect. Immun. 66, 2237-2244
   Abstract »    Full Text »    PDF »
Discrete-Event Simulation Models of Plasmodium falciparum Malaria..
F. E. McKenzie, R. C. Wong, and W. H. Bossert (1998)
SIMULATION 71, 250-261
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)