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. 1988 Jan;62(1):100–105. doi: 10.1128/jvi.62.1.100-105.1988

Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR beta chain: a means for graft rejection and immunosuppression.

R S Fujinami 1, J A Nelson 1, L Walker 1, M B Oldstone 1
PMCID: PMC250506  PMID: 2446012

Abstract

A peptide (Leu-Gly-Arg-Pro-Asp-Glu-Asp-Ser-Ser-Ser-Ser-Ser-Ser-Ser-Cys) that was identical to residues 82 through 96 of a predicted protein of 208 amino acids from the immediate-early region (IE-2) nucleic acid sequence of human cytomegalovirus was chemically synthesized. By computer analysis, the first five amino acids of this peptide showed sequence homology to the beta chain of the human histocompatibility complex HLA-DR. The homologous amino acids, 53 through 57, were located in a region that is conserved between the human DR beta chain and the beta chain of the H-2 class II histocompatibility antigen for mice. The shared region between the IE-2 protein and DR beta chain were similar in both hydrophilicity and predicted beta-turn potential. The IE-2 viral peptide induced antibodies that specifically recognized the human DR beta chain. These observations describe a protein encoded by the IE-2 region of human cytomegalovirus that contains sequence homology and shows immunologic cross-reactivity with a conserved domain of HLA-DR and suggest a mechanism to explain how human cytomegalovirus infection contributes to graft rejection after transplantation.

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Selected References

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  1. Alford C. A., Stagno S., Pass R. F. Natural history of perinatal cytomegaloviral infection. Ciba Found Symp. 1979;(77):125–147. doi: 10.1002/9780470720608.ch9. [DOI] [PubMed] [Google Scholar]
  2. Allison J. P., Ferrone S., Walker L. E., Pellegrino M. A., Silver J., Reisfeld R. A. Partial amino acid sequence of HLA-A9 antigen purified with a specific xenoantiserum. Transplantation. 1978 Dec;26(6):451–454. [PubMed] [Google Scholar]
  3. Borysiewicz L. K., Morris S., Page J. D., Sissons J. G. Human cytomegalovirus-specific cytotoxic T lymphocytes: requirements for in vitro generation and specificity. Eur J Immunol. 1983 Oct;13(10):804–809. doi: 10.1002/eji.1830131005. [DOI] [PubMed] [Google Scholar]
  4. Chou S. W. Acquisition of donor strains of cytomegalovirus by renal-transplant recipients. N Engl J Med. 1986 May 29;314(22):1418–1423. doi: 10.1056/NEJM198605293142205. [DOI] [PubMed] [Google Scholar]
  5. Demarchi J. M. Human cytomegalovirus DNA: restriction enzyme cleavage maps and map locations for immediate-early, early, and late RNAs. Virology. 1981 Oct 15;114(1):23–38. doi: 10.1016/0042-6822(81)90249-x. [DOI] [PubMed] [Google Scholar]
  6. Fujinami R. S., Oldstone M. B. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science. 1985 Nov 29;230(4729):1043–1045. doi: 10.1126/science.2414848. [DOI] [PubMed] [Google Scholar]
  7. Fujinami R. S., Oldstone M. B., Wroblewska Z., Frankel M. E., Koprowski H. Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2346–2350. doi: 10.1073/pnas.80.8.2346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hermiston T. W., Malone C. L., Witte P. R., Stinski M. F. Identification and characterization of the human cytomegalovirus immediate-early region 2 gene that stimulates gene expression from an inducible promoter. J Virol. 1987 Oct;61(10):3214–3221. doi: 10.1128/jvi.61.10.3214-3221.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jahn G., Knust E., Schmolla H., Sarre T., Nelson J. A., McDougall J. K., Fleckenstein B. Predominant immediate-early transcripts of human cytomegalovirus AD 169. J Virol. 1984 Feb;49(2):363–370. doi: 10.1128/jvi.49.2.363-370.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Larhammar D., Schenning L., Gustafsson K., Wiman K., Claesson L., Rask L., Peterson P. A. Complete amino acid sequence of an HLA-DR antigen-like beta chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, -B, and -C antigens. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3687–3691. doi: 10.1073/pnas.79.12.3687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Liu F. T., Zinnecker M., Hamaoka T., Katz D. H. New procedures for preparation and isolation of conjugates of proteins and a synthetic copolymer of D-amino acids and immunochemical characterization of such conjugates. Biochemistry. 1979 Feb 20;18(4):690–693. doi: 10.1021/bi00571a022. [DOI] [PubMed] [Google Scholar]
  12. Marglin A., Merrifield R. B. Chemical synthesis of peptides and proteins. Annu Rev Biochem. 1970;39:841–866. doi: 10.1146/annurev.bi.39.070170.004205. [DOI] [PubMed] [Google Scholar]
  13. Myers J. D., Spencer H. C., Jr, Watts J. C., Gregg M. B., Stewart J. A., Troupin R. H., Thomas E. D. Cytomegalovirus pneumonia after human marrow transplantation. Ann Intern Med. 1975 Feb;82(2):181–188. doi: 10.7326/0003-4819-82-2-181. [DOI] [PubMed] [Google Scholar]
  14. Neiman P., Wasserman P. B., Wentworth B. B., Kao G. F., Lerner K. G., Storb R., Buckner C. D., Clift R. A., Fefer A., Fass L. Interstitial pneumonia and cytomegalovirus infection as complications of human marrow transplantation. Transplantation. 1973 May;15(5):478–485. [PubMed] [Google Scholar]
  15. Quinnan G. V., Jr, Kirmani N., Esber E., Saral R., Manischewitz J. F., Rogers J. L., Rook A. H., Santos G. W., Burns W. H. HLA-restricted cytotoxic T lymphocyte and nonthymic cytotoxic lymphocyte responses to cytomegalovirus infection of bone marrow transplant recipients. J Immunol. 1981 May;126(5):2036–2041. [PubMed] [Google Scholar]
  16. Reddehase M. J., Bühring H. J., Koszinowski U. H. Cloned long-term cytolytic T-lymphocyte line with specificity for an immediate-early membrane antigen of murine cytomegalovirus. J Virol. 1986 Jan;57(1):408–412. doi: 10.1128/jvi.57.1.408-412.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reddehase M. J., Fibi M. R., Keil G. M., Koszinowski U. H. Late-phase expression of a murine cytomegalovirus immediate-early antigen recognized by cytolytic T lymphocytes. J Virol. 1986 Dec;60(3):1125–1129. doi: 10.1128/jvi.60.3.1125-1129.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rice G. P., Schrier R. D., Oldstone M. B. Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6134–6138. doi: 10.1073/pnas.81.19.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schrier R. D., Nelson J. A., Oldstone M. B. Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science. 1985 Nov 29;230(4729):1048–1051. doi: 10.1126/science.2997930. [DOI] [PubMed] [Google Scholar]
  20. Srinivasappa J., Saegusa J., Prabhakar B. S., Gentry M. K., Buchmeier M. J., Wiktor T. J., Koprowski H., Oldstone M. B., Notkins A. L. Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J Virol. 1986 Jan;57(1):397–401. doi: 10.1128/jvi.57.1.397-401.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stenberg R. M., Witte P. R., Stinski M. F. Multiple spliced and unspliced transcripts from human cytomegalovirus immediate-early region 2 and evidence for a common initiation site within immediate-early region 1. J Virol. 1985 Dec;56(3):665–675. doi: 10.1128/jvi.56.3.665-675.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Varki N. M., Reisfeld R. A., Walker L. E. Antigens associated with a human lung adenocarcinoma defined by monoclonal antibodies. Cancer Res. 1984 Feb;44(2):681–687. [PubMed] [Google Scholar]
  24. Wathen M. W., Stinski M. F. Temporal patterns of human cytomegalovirus transcription: mapping the viral RNAs synthesized at immediate early, early, and late times after infection. J Virol. 1982 Feb;41(2):462–477. doi: 10.1128/jvi.41.2.462-477.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wilson I. A., Niman H. L., Houghten R. A., Cherenson A. R., Connolly M. L., Lerner R. A. The structure of an antigenic determinant in a protein. Cell. 1984 Jul;37(3):767–778. doi: 10.1016/0092-8674(84)90412-4. [DOI] [PubMed] [Google Scholar]
  26. Wiman K., Larhammar D., Claesson L., Gustafsson K., Schenning L., Bill P., Böhme J., Denaro M., Dobberstein B., Hammerling U. Isolation and identification of a cDNA clone corresponding to an HLA-DR antigen beta chain. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1703–1707. doi: 10.1073/pnas.79.6.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. van Es A., Baldwin W. M., Oljans P. J., Tanke H. J., Ploem J. S., van Es L. A. Expression of HLA-DR on T lymphocytes following renal transplantation, and association with graft-rejection episodes and cytomegalovirus infection. Transplantation. 1984 Jan;37(1):65–69. doi: 10.1097/00007890-198401000-00018. [DOI] [PubMed] [Google Scholar]
  28. von Willebrand E., Pettersson E., Ahonen J., Häyry P. CMV infection, class II antigen expression, and human kidney allograft rejection. Transplantation. 1986 Oct;42(4):364–367. doi: 10.1097/00007890-198610000-00006. [DOI] [PubMed] [Google Scholar]

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