Abstract
Immune responses to defined antigens may differ between individuals in a population as the reflection of differences in genetic regulation. In experimental animals, variation in responsiveness to a given epitope may be due to major histocompatibility complex (HLA, in humans) class II restrictions, implying serious limitations for the development of subunit vaccines. For human populations, knowledge of the relative importance of genetic as opposed to environmental factors affecting the immune response is scarce. We have compared antibody levels after immunization through repeated infections to a major malarial antigen (Pf155/RESA) in monozygotic twins with those in dizygotic twins, siblings, or unrelated controls. Antibody responses to the intact antigen and to some of its immunodominant epitopes were found to be more concordant within monozygotic twin pairs than in dizygotic pairs or age- and sex-matched siblings living under similar environmental conditions. The results support the conclusion that the antibody responses were genetically regulated. When the responses were assessed for possible associations with different HLA class II DRB, DQA, and DQB alleles had haplotypes, no associations were found. This suggests that the regulation of the Pf155/RESA antibody responses seen in this study reflects the impact of factors encoded by genes outside the HLA class II regions.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alper C. A., Kruskall M. S., Marcus-Bagley D., Craven D. E., Katz A. J., Brink S. J., Dienstag J. L., Awdeh Z., Yunis E. J. Genetic prediction of nonresponse to hepatitis B vaccine. N Engl J Med. 1989 Sep 14;321(11):708–712. doi: 10.1056/NEJM198909143211103. [DOI] [PubMed] [Google Scholar]
- Berzins K., Perlmann H., Wåhlin B., Carlsson J., Wahlgren M., Udomsangpetch R., Björkman A., Patarroyo M. E., Perlmann P. Rabbit and human antibodies to a repeated amino acid sequence of a Plasmodium falciparum antigen, Pf 155, react with the native protein and inhibit merozoite invasion. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1065–1069. doi: 10.1073/pnas.83.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Björkman A., Hedman P., Brohult J., Willcox M., Diamant I., Pehrsson P. O., Rombo L., Bengtsson E. Different malaria control activities in an area of Liberia--effects on malariometric parameters. Ann Trop Med Parasitol. 1985 Jun;79(3):239–246. doi: 10.1080/00034983.1985.11811914. [DOI] [PubMed] [Google Scholar]
- Björkman A., Perlmann H., Petersen E., Hogh B., Lebbad M., Warsame M., Hanson A. P., Perlmann P. Consecutive determinations of seroreactivities to Pf 155/RESA antigen and to its different repetitive sequences in adult men from a holoendemic area of Liberia. Parasite Immunol. 1990 Mar;12(2):115–123. doi: 10.1111/j.1365-3024.1990.tb00941.x. [DOI] [PubMed] [Google Scholar]
- Chougnet C., Deloron P., Lepers J. P., Tallet S., Rason M. D., Astagneau P., Savel J., Coulanges P. Humoral and cell-mediated immune responses to the Plasmodium falciparum antigens PF155/RESA and CS protein: seasonal variations in a population recently reexposed to endemic malaria. Am J Trop Med Hyg. 1990 Sep;43(3):234–242. doi: 10.4269/ajtmh.1990.43.234. [DOI] [PubMed] [Google Scholar]
- Chougnet C., Troye-Blomberg M., Deloron P., Kabilan L., Lepers J. P., Savel J., Perlmann P. Human immune response in Plasmodium falciparum malaria. Synthetic peptides corresponding to known epitopes of the Pf155/RESA antigen induce production of parasite-specific antibodies in vitro. J Immunol. 1991 Oct 1;147(7):2295–2301. [PubMed] [Google Scholar]
- Coppel R. L., Cowman A. F., Anders R. F., Bianco A. E., Saint R. B., Lingelbach K. R., Kemp D. J., Brown G. V. Immune sera recognize on erythrocytes Plasmodium falciparum antigen composed of repeated amino acid sequences. 1984 Aug 30-Sep 5Nature. 310(5980):789–792. doi: 10.1038/310789a0. [DOI] [PubMed] [Google Scholar]
- Corradin G. Antigen processing and presentation. Immunol Lett. 1990 Aug;25(1-3):11–13. doi: 10.1016/0165-2478(90)90082-2. [DOI] [PubMed] [Google Scholar]
- Fontenille D., Lepers J. P., Campbell G. H., Coluzzi M., Rakotoarivony I., Coulanges P. Malaria transmission and vector biology in Manarintsoa, high plateaux of Madagascar. Am J Trop Med Hyg. 1990 Aug;43(2):107–115. doi: 10.4269/ajtmh.1990.43.107. [DOI] [PubMed] [Google Scholar]
- Goerlich R., Häcker G., Pfeffer K., Heeg K., Wagner H. Plasmodium falciparum merozoites primarily stimulate the V gamma 9 subset of human gamma/delta T cells. Eur J Immunol. 1991 Oct;21(10):2613–2616. doi: 10.1002/eji.1830211045. [DOI] [PubMed] [Google Scholar]
- Hill A. V., Allsopp C. E., Kwiatkowski D., Anstey N. M., Twumasi P., Rowe P. A., Bennett S., Brewster D., McMichael A. J., Greenwood B. M. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991 Aug 15;352(6336):595–600. doi: 10.1038/352595a0. [DOI] [PubMed] [Google Scholar]
- Ho M., Webster H. K., Tongtawe P., Pattanapanyasat K., Weidanz W. P. Increased gamma delta T cells in acute Plasmodium falciparum malaria. Immunol Lett. 1990 Aug;25(1-3):139–141. doi: 10.1016/0165-2478(90)90105-y. [DOI] [PubMed] [Google Scholar]
- Kabilan L., Troye-Blomberg M., Patarroyo M. E., Björkman A., Perlmann P. Regulation of the immune response in Plasmodium falciparum malaria: IV. T cell dependent production of immunoglobulin and anti-P. falciparum antibodies in vitro. Clin Exp Immunol. 1987 May;68(2):288–297. [PMC free article] [PubMed] [Google Scholar]
- Lepers J. P., Deloron P., Andriamagatiana-Rason M. D., Ramanamirija J. A., Coulanges P. Newly transmitted Plasmodium falciparum malaria in the central highland plateaux of Madagascar: assessment of clinical impact in a rural community. Bull World Health Organ. 1990;68(2):217–222. [PMC free article] [PubMed] [Google Scholar]
- Lepers J. P., Deloron P., Fontenille D., Coulanges P. Reappearance of falciparum malaria in central highland plateaux of Madagascar. Lancet. 1988 Mar 12;1(8585):586–586. doi: 10.1016/s0140-6736(88)91375-x. [DOI] [PubMed] [Google Scholar]
- Lew A. M., Langford C. J., Pye D., Edwards S., Corcoran L., Anders R. F. Class II restriction in mice to the malaria candidate vaccine ring infected erythrocyte surface antigen (RESA) as synthetic peptides or as expressed in recombinant vaccinia. J Immunol. 1989 Jun 1;142(11):4012–4016. [PubMed] [Google Scholar]
- Mattei D., Berzins K., Wahlgren M., Udomsangpetch R., Perlmann P., Griesser H. W., Scherf A., Müller-Hill B., Bonnefoy S., Guillotte M. Cross-reactive antigenic determinants present on different Plasmodium falciparum blood-stage antigens. Parasite Immunol. 1989 Jan;11(1):15–29. doi: 10.1111/j.1365-3024.1989.tb00645.x. [DOI] [PubMed] [Google Scholar]
- Olerup O., Troye-Blomberg M., Schreuder G. M., Riley E. M. HLA-DR and -DQ gene polymorphism in West Africans is twice as extensive as in north European Caucasians: evolutionary implications. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8480–8484. doi: 10.1073/pnas.88.19.8480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perlmann H., Berzins K., Wahlgren M., Carlsson J., Björkman A., Patarroyo M. E., Perlmann P. Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum. J Exp Med. 1984 Jun 1;159(6):1686–1704. doi: 10.1084/jem.159.6.1686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perlmann H., Perlmann P., Berzins K., Wåhlin B., Troye-Blomberg M., Hagstedt M., Andersson I., Högh B., Petersen E., Björkman A. Dissection of the human antibody response to the malaria antigen Pf155/RESA into epitope specific components. Immunol Rev. 1989 Dec;112:115–132. doi: 10.1111/j.1600-065x.1989.tb00555.x. [DOI] [PubMed] [Google Scholar]
- Petersen E., Høgh B., Marbiah N. T., Perlmann H., Willcox M., Dolopaie E., Hanson A. P., Björkman A., Perlmann P. A longitudinal study of antibodies to the Plasmodium falciparum antigen Pf155/RESA and immunity to malaria infection in adult Liberians. Trans R Soc Trop Med Hyg. 1990 May-Jun;84(3):339–345. doi: 10.1016/0035-9203(90)90307-z. [DOI] [PubMed] [Google Scholar]
- Riley E. M., Allen S. J., Troye-Blomberg M., Bennett S., Perlmann H., Andersson G., Smedman L., Perlmann P., Greenwood B. M. Association between immune recognition of the malaria vaccine candidate antigen Pf155/RESA and resistance to clinical disease: a prospective study in a malaria-endemic region of west Africa. Trans R Soc Trop Med Hyg. 1991 Jul-Aug;85(4):436–443. doi: 10.1016/0035-9203(91)90207-f. [DOI] [PubMed] [Google Scholar]
- Riley E. M., Ong C. S., Olerup O., Eida S., Allen S. J., Bennett S., Andersson G., Targett G. A. Cellular and humoral immune responses to Plasmodium falciparum gametocyte antigens in malaria-immune individuals. Limited response to the 48/45-kilodalton surface antigen does not appear to be due to MHC restriction. J Immunol. 1990 Jun 15;144(12):4810–4816. [PubMed] [Google Scholar]
- Troye-Blomberg M., Olerup O., Larsson A., Sjöberg K., Perlmann H., Riley E., Lepers J. P., Perlmann P. Failure to detect MHC class II associations of the human immune response induced by repeated malaria infections to the Plasmodium falciparum antigen Pf155/RESA. Int Immunol. 1991 Oct;3(10):1043–1051. doi: 10.1093/intimm/3.10.1043. [DOI] [PubMed] [Google Scholar]
- Wassom D. L., Kelly E. A. The role of the major histocompatibility complex in resistance to parasite infections. Crit Rev Immunol. 1990;10(1):31–52. [PubMed] [Google Scholar]
- Weiss W. R., Good M. F., Hollingdale M. R., Miller L. H., Berzofsky J. A. Genetic control of immunity to Plasmodium yoelii sporozoites. J Immunol. 1989 Dec 15;143(12):4263–4266. [PubMed] [Google Scholar]