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. 1995 Nov 1;182(5):1435–1445. doi: 10.1084/jem.182.5.1435

Irradiated sporozoite vaccine induces HLA-B8-restricted cytotoxic T lymphocyte responses against two overlapping epitopes of the Plasmodium falciparum sporozoite surface protein 2

PMCID: PMC2192212  PMID: 7595214

Abstract

Vaccines designed to protect against malaria by inducing CD8+ cytotoxic T lymphocytes (CTL) in individuals of diverse HLA backgrounds must contain multiple conserved epitopes from various preerythrocytic-stage antigens. Plasmodium falciparum sporozoite surface protein 2 (PfSSP2) is considered an important antigen for inclusion in such vaccines, because CD8+ CTL against the P. yoelii SSP2 protect mice against malaria by eliminating infected hepatocytes. To develop PfSSP2 as a component of malaria vaccines, we investigated the presence of anti- PfSSP2 CTL in two HLA-B8+ volunteers immunized with irradiated P. falciparum sporozoites and characterized their CTL responses using PfSSP2-derived 15-amino acid peptides bearing the HLA-B8-binding motif. Peripheral blood mononuclear cells from both volunteers stimulated with recombinant vaccinia expressing PfSSP2 displayed antigen-specific, genetically restricted, CD8+ T cell-dependent CTL activity against autologous target cells expressing PfSSP2. Of the five HLA-B8 motif- bearing 15-mers identified in the PfSSP2 sequence, two peptides sharing a 10-amino acid overlap sensitized HLA-B8-matched target cells from both volunteers for lysis by peptide-stimulated effectors. The CTL activity was HLA-B8 restricted and dependent on CD8+ T cells. Analysis of the three shorter peptides representing HLA-B8 motif-bearing sequences within the two positive peptides for their ability to bind to HLA-B8 in vitro, and to sensitize target cells for lysis by effectors stimulated with the 15-mers, identified two overlapping HLA-B8- restricted CTL epitopes. Available data indicate that the sequence of one CTL epitope is conserved and the other is variant among P. falciparum isolates. Circulating activated CTL against the conserved epitope could be directly identified in one of the two volunteers. The identification of two HLA-B8-restricted CTL epitopes on PfSSP2 provides data critical to developing an epitope-based anti-liver stage malaria vaccine.

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Selected References

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  1. Aidoo M., Lalvani A., Allsopp C. E., Plebanski M., Meisner S. J., Krausa P., Browning M., Morris-Jones S., Gotch F., Fidock D. A. Identification of conserved antigenic components for a cytotoxic T lymphocyte-inducing vaccine against malaria. Lancet. 1995 Apr 22;345(8956):1003–1007. doi: 10.1016/s0140-6736(95)90754-8. [DOI] [PubMed] [Google Scholar]
  2. Bertoletti A., Ferrari C., Fiaccadori F., Penna A., Margolskee R., Schlicht H. J., Fowler P., Guilhot S., Chisari F. V. HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10445–10449. doi: 10.1073/pnas.88.23.10445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burrows S. R., Rodda S. J., Suhrbier A., Geysen H. M., Moss D. J. The specificity of recognition of a cytotoxic T lymphocyte epitope. Eur J Immunol. 1992 Jan;22(1):191–195. doi: 10.1002/eji.1830220128. [DOI] [PubMed] [Google Scholar]
  4. Clyde D. F. Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am J Trop Med Hyg. 1975 May;24(3):397–401. doi: 10.4269/ajtmh.1975.24.397. [DOI] [PubMed] [Google Scholar]
  5. Clyde D. F., McCarthy V. C., Miller R. M., Hornick R. B. Specificity of protection of man immunized against sporozoite-induced falciparum malaria. Am J Med Sci. 1973 Dec;266(6):398–403. doi: 10.1097/00000441-197312000-00001. [DOI] [PubMed] [Google Scholar]
  6. Dame J. B., Williams J. L., McCutchan T. F., Weber J. L., Wirtz R. A., Hockmeyer W. T., Maloy W. L., Haynes J. D., Schneider I., Roberts D. Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science. 1984 Aug 10;225(4662):593–599. doi: 10.1126/science.6204383. [DOI] [PubMed] [Google Scholar]
  7. DiBrino M., Parker K. C., Shiloach J., Knierman M., Lukszo J., Turner R. V., Biddison W. E., Coligan J. E. Endogenous peptides bound to HLA-A3 possess a specific combination of anchor residues that permit identification of potential antigenic peptides. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1508–1512. doi: 10.1073/pnas.90.4.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DiBrino M., Parker K. C., Shiloach J., Turner R. V., Tsuchida T., Garfield M., Biddison W. E., Coligan J. E. Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8. J Immunol. 1994 Jan 15;152(2):620–631. [PubMed] [Google Scholar]
  9. DiBrino M., Tsuchida T., Turner R. V., Parker K. C., Coligan J. E., Biddison W. E. HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. J Immunol. 1993 Dec 1;151(11):5930–5935. [PubMed] [Google Scholar]
  10. Doolan D. L., Houghten R. A., Good M. F. Location of human cytotoxic T cell epitopes within a polymorphic domain of the Plasmodium falciparum circumsporozoite protein. Int Immunol. 1991 Jun;3(6):511–516. doi: 10.1093/intimm/3.6.511. [DOI] [PubMed] [Google Scholar]
  11. Edelman R., Hoffman S. L., Davis J. R., Beier M., Sztein M. B., Losonsky G., Herrington D. A., Eddy H. A., Hollingdale M. R., Gordon D. M. Long-term persistence of sterile immunity in a volunteer immunized with X-irradiated Plasmodium falciparum sporozoites. J Infect Dis. 1993 Oct;168(4):1066–1070. doi: 10.1093/infdis/168.4.1066. [DOI] [PubMed] [Google Scholar]
  12. Egan J. E., Hoffman S. L., Haynes J. D., Sadoff J. C., Schneider I., Grau G. E., Hollingdale M. R., Ballou W. R., Gordon D. M. Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 1993 Aug;49(2):166–173. doi: 10.4269/ajtmh.1993.49.166. [DOI] [PubMed] [Google Scholar]
  13. Engelhard V. H. Structure of peptides associated with class I and class II MHC molecules. Annu Rev Immunol. 1994;12:181–207. doi: 10.1146/annurev.iy.12.040194.001145. [DOI] [PubMed] [Google Scholar]
  14. Falk K., Rötzschke O., Grahovac B., Schendel D., Stevanović S., Gnau V., Jung G., Strominger J. L., Rammensee H. G. Allele-specific peptide ligand motifs of HLA-C molecules. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):12005–12009. doi: 10.1073/pnas.90.24.12005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Falo L. D., Jr, Colarusso L. J., Benacerraf B., Rock K. L. Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8347–8350. doi: 10.1073/pnas.89.17.8347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fidock D. A., Bottius E., Brahimi K., Moelans I. I., Aikawa M., Konings R. N., Certa U., Olafsson P., Kaidoh T., Asavanich A. Cloning and characterization of a novel Plasmodium falciparum sporozoite surface antigen, STARP. Mol Biochem Parasitol. 1994 Apr;64(2):219–232. doi: 10.1016/0166-6851(94)00012-3. [DOI] [PubMed] [Google Scholar]
  17. Fidock D. A., Gras-Masse H., Lepers J. P., Brahimi K., Benmohamed L., Mellouk S., Guerin-Marchand C., Londono A., Raharimalala L., Meis J. F. Plasmodium falciparum liver stage antigen-1 is well conserved and contains potent B and T cell determinants. J Immunol. 1994 Jul 1;153(1):190–204. [PubMed] [Google Scholar]
  18. Gotch F. M., Nixon D. F., Alp N., McMichael A. J., Borysiewicz L. K. High frequency of memory and effector gag specific cytotoxic T lymphocytes in HIV seropositive individuals. Int Immunol. 1990;2(8):707–712. doi: 10.1093/intimm/2.8.707. [DOI] [PubMed] [Google Scholar]
  19. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gwadz R. W., Cochrane A. H., Nussenzweig V., Nussenzweig R. S. Preliminary studies on vaccination of rhesus monkeys with irradiated sporozoites of Plasmodium knowlesi and characterization of surface antigens of these parasites. Bull World Health Organ. 1979;57 (Suppl 1):165–173. [PMC free article] [PubMed] [Google Scholar]
  21. Hariharan I. K., Adams J. M. cDNA sequence for human bcr, the gene that translocates to the abl oncogene in chronic myeloid leukaemia. EMBO J. 1987 Jan;6(1):115–119. doi: 10.1002/j.1460-2075.1987.tb04727.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hill A. V., Elvin J., Willis A. C., Aidoo M., Allsopp C. E., Gotch F. M., Gao X. M., Takiguchi M., Greenwood B. M., Townsend A. R. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature. 1992 Dec 3;360(6403):434–439. doi: 10.1038/360434a0. [DOI] [PubMed] [Google Scholar]
  23. Hoffman S. L., Isenbarger D., Long G. W., Sedegah M., Szarfman A., Waters L., Hollingdale M. R., van der Meide P. H., Finbloom D. S., Ballou W. R. Sporozoite vaccine induces genetically restricted T cell elimination of malaria from hepatocytes. Science. 1989 Jun 2;244(4908):1078–1081. doi: 10.1126/science.2524877. [DOI] [PubMed] [Google Scholar]
  24. Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Huczko E. L., Bodnar W. M., Benjamin D., Sakaguchi K., Zhu N. Z., Shabanowitz J., Henderson R. A., Appella E., Hunt D. F., Engelhard V. H. Characteristics of endogenous peptides eluted from the class I MHC molecule HLA-B7 determined by mass spectrometry and computer modeling. J Immunol. 1993 Sep 1;151(5):2572–2587. [PubMed] [Google Scholar]
  26. Johnson R. P., Trocha A., Buchanan T. M., Walker B. D. Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation. J Exp Med. 1992 Apr 1;175(4):961–971. doi: 10.1084/jem.175.4.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Khusmith S., Charoenvit Y., Kumar S., Sedegah M., Beaudoin R. L., Hoffman S. L. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science. 1991 May 3;252(5006):715–718. doi: 10.1126/science.1827210. [DOI] [PubMed] [Google Scholar]
  28. Khusmith S., Sedegah M., Hoffman S. L. Complete protection against Plasmodium yoelii by adoptive transfer of a CD8+ cytotoxic T-cell clone recognizing sporozoite surface protein 2. Infect Immun. 1994 Jul;62(7):2979–2983. doi: 10.1128/iai.62.7.2979-2983.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kozlowski S., Corr M., Takeshita T., Boyd L. F., Pendleton C. D., Germain R. N., Berzofsky J. A., Margulies D. H. Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules. J Exp Med. 1992 Jun 1;175(6):1417–1422. doi: 10.1084/jem.175.6.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kubo R. T., Sette A., Grey H. M., Appella E., Sakaguchi K., Zhu N. Z., Arnott D., Sherman N., Shabanowitz J., Michel H. Definition of specific peptide motifs for four major HLA-A alleles. J Immunol. 1994 Apr 15;152(8):3913–3924. [PubMed] [Google Scholar]
  31. Kumar S., Miller L. H., Quakyi I. A., Keister D. B., Houghten R. A., Maloy W. L., Moss B., Berzofsky J. A., Good M. F. Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum. Nature. 1988 Jul 21;334(6179):258–260. doi: 10.1038/334258a0. [DOI] [PubMed] [Google Scholar]
  32. Malik A., Egan J. E., Houghten R. A., Sadoff J. C., Hoffman S. L. Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3300–3304. doi: 10.1073/pnas.88.8.3300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mazier D., Mellouk S., Beaudoin R. L., Texier B., Druilhe P., Hockmeyer W., Trosper J., Paul C., Charoenvit Y., Young J. Effect of antibodies to recombinant and synthetic peptides on P. falciparum sporozoites in vitro. Science. 1986 Jan 10;231(4734):156–159. doi: 10.1126/science.3510455. [DOI] [PubMed] [Google Scholar]
  34. Nussenzweig R. S., Vanderberg J., Most H., Orton C. Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature. 1967 Oct 14;216(5111):160–162. doi: 10.1038/216160a0. [DOI] [PubMed] [Google Scholar]
  35. Pamer E. G., Harty J. T., Bevan M. J. Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature. 1991 Oct 31;353(6347):852–855. doi: 10.1038/353852a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Parker K. C., Carreno B. M., Sestak L., Utz U., Biddison W. E., Coligan J. E. Peptide binding to HLA-A2 and HLA-B27 isolated from Escherichia coli. Reconstitution of HLA-A2 and HLA-B27 heavy chain/beta 2-microglobulin complexes requires specific peptides. J Biol Chem. 1992 Mar 15;267(8):5451–5459. [PubMed] [Google Scholar]
  37. Parker K. C., DiBrino M., Hull L., Coligan J. E. The beta 2-microglobulin dissociation rate is an accurate measure of the stability of MHC class I heterotrimers and depends on which peptide is bound. J Immunol. 1992 Sep 15;149(6):1896–1904. [PubMed] [Google Scholar]
  38. Phillips R. E., Rowland-Jones S., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991 Dec 12;354(6353):453–459. doi: 10.1038/354453a0. [DOI] [PubMed] [Google Scholar]
  39. Ponnudurai T., Leeuwenberg A. D., Meuwissen J. H. Chloroquine sensitivity of isolates of Plasmodium falciparum adapted to in vitro culture. Trop Geogr Med. 1981 Mar;33(1):50–54. [PubMed] [Google Scholar]
  40. Rieckmann K. H., Beaudoin R. L., Cassells J. S., Sell K. W. Use of attenuated sporozoites in the immunization of human volunteers against falciparum malaria. Bull World Health Organ. 1979;57 (Suppl 1):261–265. [PMC free article] [PubMed] [Google Scholar]
  41. Rieckmann K. H., Carson P. E., Beaudoin R. L., Cassells J. S., Sell K. W. Letter: Sporozoite induced immunity in man against an Ethiopian strain of Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1974;68(3):258–259. doi: 10.1016/0035-9203(74)90129-1. [DOI] [PubMed] [Google Scholar]
  42. Robson K. J., Hall J. R., Davies L. C., Crisanti A., Hill A. V., Wellems T. E. Polymorphism of the TRAP gene of Plasmodium falciparum. Proc Biol Sci. 1990 Dec 22;242(1305):205–216. doi: 10.1098/rspb.1990.0126. [DOI] [PubMed] [Google Scholar]
  43. Robson K. J., Hall J. R., Jennings M. W., Harris T. J., Marsh K., Newbold C. I., Tate V. E., Weatherall D. J. A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature. 1988 Sep 1;335(6185):79–82. doi: 10.1038/335079a0. [DOI] [PubMed] [Google Scholar]
  44. Rodrigues M. M., Cordey A. S., Arreaza G., Corradin G., Romero P., Maryanski J. L., Nussenzweig R. S., Zavala F. CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria. Int Immunol. 1991 Jun;3(6):579–585. doi: 10.1093/intimm/3.6.579. [DOI] [PubMed] [Google Scholar]
  45. Rogers W. O., Malik A., Mellouk S., Nakamura K., Rogers M. D., Szarfman A., Gordon D. M., Nussler A. K., Aikawa M., Hoffman S. L. Characterization of Plasmodium falciparum sporozoite surface protein 2. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9176–9180. doi: 10.1073/pnas.89.19.9176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Romero P., Maryanski J. L., Corradin G., Nussenzweig R. S., Nussenzweig V., Zavala F. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989 Sep 28;341(6240):323–326. doi: 10.1038/341323a0. [DOI] [PubMed] [Google Scholar]
  47. Rosario V. Cloning of naturally occurring mixed infections of malaria parasites. Science. 1981 May 29;212(4498):1037–1038. doi: 10.1126/science.7015505. [DOI] [PubMed] [Google Scholar]
  48. Ruppert J., Sidney J., Celis E., Kubo R. T., Grey H. M., Sette A. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 1993 Sep 10;74(5):929–937. doi: 10.1016/0092-8674(93)90472-3. [DOI] [PubMed] [Google Scholar]
  49. Sanchez G. I., Rogers W. O., Mellouk S., Hoffman S. L. Plasmodium falciparum: exported protein-1, a blood stage antigen, is expressed in liver stage parasites. Exp Parasitol. 1994 Aug;79(1):59–62. doi: 10.1006/expr.1994.1060. [DOI] [PubMed] [Google Scholar]
  50. Schofield L., Villaquiran J., Ferreira A., Schellekens H., Nussenzweig R., Nussenzweig V. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 1987 Dec 17;330(6149):664–666. doi: 10.1038/330664a0. [DOI] [PubMed] [Google Scholar]
  51. Sedegah M., Sim B. K., Mason C., Nutman T., Malik A., Roberts C., Johnson A., Ochola J., Koech D., Were B. Naturally acquired CD8+ cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. J Immunol. 1992 Aug 1;149(3):966–971. [PubMed] [Google Scholar]
  52. Sette A., Sidney J., del Guercio M. F., Southwood S., Ruppert J., Dahlberg C., Grey H. M., Kubo R. T. Peptide binding to the most frequent HLA-A class I alleles measured by quantitative molecular binding assays. Mol Immunol. 1994 Aug;31(11):813–822. doi: 10.1016/0161-5890(94)90019-1. [DOI] [PubMed] [Google Scholar]
  53. Storkus W. J., Howell D. N., Salter R. D., Dawson J. R., Cresswell P. NK susceptibility varies inversely with target cell class I HLA antigen expression. J Immunol. 1987 Mar 15;138(6):1657–1659. [PubMed] [Google Scholar]
  54. Sugden B., Mark W. Clonal transformation of adult human leukocytes by Epstein-Barr virus. J Virol. 1977 Sep;23(3):503–508. doi: 10.1128/jvi.23.3.503-508.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Suhrbier A., Schmidt C., Fernan A. Prediction of an HLA B8-restricted influenza epitope by motif. Immunology. 1993 May;79(1):171–173. [PMC free article] [PubMed] [Google Scholar]
  56. Sutton J., Rowland-Jones S., Rosenberg W., Nixon D., Gotch F., Gao X. M., Murray N., Spoonas A., Driscoll P., Smith M. A sequence pattern for peptides presented to cytotoxic T lymphocytes by HLA B8 revealed by analysis of epitopes and eluted peptides. Eur J Immunol. 1993 Feb;23(2):447–453. doi: 10.1002/eji.1830230222. [DOI] [PubMed] [Google Scholar]
  57. Walker B. D., Flexner C., Birch-Limberger K., Fisher L., Paradis T. J., Aldovini A., Young R., Moss B., Schooley R. T. Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9514–9518. doi: 10.1073/pnas.86.23.9514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Weiss W. R., Berzofsky J. A., Houghten R. A., Sedegah M., Hollindale M., Hoffman S. L. A T cell clone directed at the circumsporozoite protein which protects mice against both Plasmodium yoelii and Plasmodium berghei. J Immunol. 1992 Sep 15;149(6):2103–2109. [PubMed] [Google Scholar]
  59. Weiss W. R., Sedegah M., Beaudoin R. L., Miller L. H., Good M. F. CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A. 1988 Jan;85(2):573–576. doi: 10.1073/pnas.85.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Wizel B., Houghten R., Church P., Tine J. A., Lanar D. E., Gordon D. M., Ballou W. R., Sette A., Hoffman S. L. HLA-A2-restricted cytotoxic T lymphocyte responses to multiple Plasmodium falciparum sporozoite surface protein 2 epitopes in sporozoite-immunized volunteers. J Immunol. 1995 Jul 15;155(2):766–775. [PubMed] [Google Scholar]
  61. Wizel B., Rogers W. O., Houghten R. A., Lanar D. E., Tine J. A., Hoffman S. L. Induction of murine cytotoxic T lymphocytes against Plasmodium falciparum sporozoite surface protein 2. Eur J Immunol. 1994 Jul;24(7):1487–1495. doi: 10.1002/eji.1830240705. [DOI] [PubMed] [Google Scholar]
  62. Zemmour J., Little A. M., Schendel D. J., Parham P. The HLA-A,B "negative" mutant cell line C1R expresses a novel HLA-B35 allele, which also has a point mutation in the translation initiation codon. J Immunol. 1992 Mar 15;148(6):1941–1948. [PubMed] [Google Scholar]

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