Skip to main content
NCBI home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2004 Feb 10;191(2):680–686. doi: 10.1016/0042-6822(92)90243-I

Characterization of the specificity and genetic restriction of human CD4+ cytotoxic T cell clones reactive to capsid antigen of rubella virus

Dawei Ou ∗, Pele Chong †, Paul McVeish †, Wilfred A Jefferies ‡, Shirley Gillam ∗,1
PMCID: PMC7131658  PMID: 1280381

Abstract

Using 11 overlapping synthetic peptides covering more than 95% of the amino acid sequence of capsid protein of rubella virus, 7 CD4+ T cell clones (R10, R11, R18, A2, A10, A1, and A12) isolated from 2 rubella seropositive donors reacted strongly to rubella capsid peptides C6 (residues 119–152), C9 (residues 205–233), or C11 (residues 255–280), respectively, in both proliferation and cytotoxicity assay. Truncated peptides C6E (residues 125–139), C9B (residues 205–216), and C11E (residues 260–272) were shown to be involved directly to the T cell determinants of C6, C9, and C11, respectively. Genetic restriction of these T cell clones was analyzed by using human cell lines with various HLA-DR phenotypes as targets and/or antigen-presenting cells in cytotoxicity assay and/or proliferation assays. The results indicated that the recognition of peptide C6 by T cell clones (R11 and R18) was associated with DRw9 molecule, while the HLA restriction element of the responses of other T cell clones (A2 and A11, A10, and A12) that reacted with peptide C9 or C11 was DR4 molecule. However, there may be a cross-recognition by the T cell clone (A12) between DR1 and DR4 subtypes.

References

  1. Berzofsky J.A. Immunodominance of T-cell epitopes: Applications to vaccine design. In: Lerner R.A., Ginsberg H., Chanock R.M., Brown F., editors. Vaccines 89. Modern Approaches to New Vaccines Including Prevention of AIDS. Cold Spring Harbor Laboratory; Cold Spring Harbor, NY: 1989. pp. 27–31. [Google Scholar]
  2. Brett S.J., Blau J., Hughes-Jenkins C.M., Rhodes J., Liew F.Y., Tite J.P. Human T cell recognition of influenza A nucleoprotein: Specificity and genetic restriction of immunodominant T helper cell epitopes. J. Immunol. 1991;147:984–991. [PubMed] [Google Scholar]
  3. Brodsky F.M., Parham P. Monomorphic anti-HLA-A, B, C monoclonal antibodies detecting molecular subunits and combinatorial determinants. J. Immunol. 1982;128:129. [PubMed] [Google Scholar]
  4. Celis E., Ou D., Otvos L., Jr. Recognition of hepatitis B surface antigen by human T lymphocytes: Proliferative and cytotoxic responses to major antigenic determinant defined by synthetic peptides. J. Immunol. 1988;140:1808–1815. [PubMed] [Google Scholar]
  5. Celis E., Ou D., Dietzschold B., Koprowski H. Recognition of rabies and rabies-related virus by T cell derived from human vaccine recipients. J. Virol. 1988;62:3128–3134. doi: 10.1128/jvi.62.9.3128-3134.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chantler J.K., Ford D.K., Tingle A.J. Persistent rubella infection and rubella-associated arthritis. Lancet. 1982;1:1323–1325. doi: 10.1016/s0140-6736(82)92398-4. [DOI] [PubMed] [Google Scholar]
  7. Clarke D.M., Loo T.W., Hui I., Chong P., Gillam S. Nucleotide sequence and in vitro expression of rubella virus 24S subgenomic messenger RNA encoding the structural proteins E1, E2 and C. Nucleic Acids Res. 1987;15:3041–3057. doi: 10.1093/nar/15.7.3041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Lisl C., Berzofsky J.A. Vol. 82. 1985. T-cell antigenic sites to be amphipathic structures; pp. 7048–7052. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fayolle C., Deriaud E., Leclerc C. In vivo induction of cytotoxic T cell response by a free synthetic peptide requires CD4+ T cell help. J. Immunol. 1991;147:4069–4073. [PubMed] [Google Scholar]
  10. Fraser J.R.E., Cunningham A.L., Hayes K., Leach R., Lunt R. Rubella arthritis in adults. Isolation of virus, cytology and other aspects of synovial reaction. Clin. Exp. Rheumatol. 1983;1:287–293. [PubMed] [Google Scholar]
  11. Giles R.C., Nunez G., Hurley C.K., Nunez-Roldan A., Winchester R., Stastny P., Capra J.D. Structural analysis of a human I-A Homologue using a monoclonal antibody that recognizes an MB3-like specificity. J. Exp. Med. 1983;157:1461–1470. doi: 10.1084/jem.157.5.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Giles R.C., Capra J.D. Structure, function, and Genetics of Human Class II Molecules. Adv. Immunol. 1985;37:1–71. doi: 10.1016/s0065-2776(08)60337-5. [DOI] [PubMed] [Google Scholar]
  13. Good M.F., Berzofsky J.A., Miller L.H. The T cell response to the malaria circumsporozoite protein: An immunological approach to vaccine development. Annu. Rev. Immunol. 1988;6:663–688. doi: 10.1146/annurev.iy.06.040188.003311. [DOI] [PubMed] [Google Scholar]
  14. Korner H., Schliephake A., Winter J., Zimprich F., Lassmann H., Sedgwick J., Siddell S., Wege H. Nucleocapsid or spike protein-specific CD4+T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+T cells. J. Immunol. 1991;147:2317–2323. [PubMed] [Google Scholar]
  15. Lamb J., Rees A.D.M., Bal V., Ikeda H., Wilkinson D., De Vries R.R.P., Rothbard J.B. Prediction and identification of an HLA-DR restricted T cell determinant in the 19 KDa protein of Mycobacterium tuberculosis. Eur. J. Immunol. 1988;18:973. doi: 10.1002/eji.1830180623. [DOI] [PubMed] [Google Scholar]
  16. Lampson L.A., Levy R. Two populations of la-like molecules on a human B cell line. J. Immunol. 1980;125:293. [PubMed] [Google Scholar]
  17. Lombardi G., Sidhu S., Batchelor J.R., Lechler R.I. Vol. 86. 1989. Allorecognition of DR1 by T cell from a DR4/DRw13 responder mimics self-restricted recognition of endogenous peptide; pp. 4190–4194. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Margalit H., Cornette J.L., Cease K.B., Delisi C., Berzofsky J.A. Prediction of Immunodominant helper T cell antigenic sites from the primary sequence. J. Immunol. 1987;138:2213. [PubMed] [Google Scholar]
  19. Marsh S.G.E., Bodmer J.G. HLA-DR and DQ epitopes and monoclonal antibody specificity. Immunol. Today. 1989;10:305–312. doi: 10.1016/0167-5699(89)90086-8. [DOI] [PubMed] [Google Scholar]
  20. Milich D.R., McLachlin A., Thornton G.B., Hughes J.L. Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site. Nature (London) 1987;329:547–549. doi: 10.1038/329547a0. [DOI] [PubMed] [Google Scholar]
  21. Milich D.R. Synthetic T and B cell recognition sites: Implications for vaccine development. Adv. Immunol. 1988;45:195–281. doi: 10.1016/s0065-2776(08)60694-x. [DOI] [PubMed] [Google Scholar]
  22. Oker-Blom, Kalkkinen C.N., Kaariainen L., Pettersson R.F. Rubella virus contain one capsid protein and three envelope glycoprotein, E1, E2a and E2b. J. Virol. 1983;46:964–973. doi: 10.1128/jvi.46.3.964-973.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ou D., Chong P., Tripet B., Gillam S. Analysis of T- and B-cell epitopes of capsid protein of rubella virus by using synthetic peptide. J. Virol. 1992;66:1674–1681. doi: 10.1128/jvi.66.3.1674-1681.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Perfins F.T. Licensed vaccines. Rev. Infect. Dis. 1985;7:573–576. doi: 10.1093/clinids/7.supplement_1.s73. [DOI] [PubMed] [Google Scholar]
  25. Rees A.D.M., Lombardi G., Scoging A., Barber L., Mitchell D., Lamb J., Lechler R.I. Functional evidence for the recognition of endogenous peptides by autoreactive T cell clones. Int. Immunol. 1989;1:624. doi: 10.1093/intimm/1.6.624. [DOI] [PubMed] [Google Scholar]
  26. Rothbard J.B., Taylor W.R. A sequence pattern common to T cell epitopes. EMBO J. 1988;7:93. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sandra W.B., Stetler H.C., Preblud S.R., Williams N.M., Orenstein W.A., Bart K.J., Hinman A.R., Herrmann K.L. Fetal risk associated with rubella vaccine: An update. Rev. Infect. Dis. 1985;7:S95–S102. doi: 10.1093/clinids/7.supplement_1.s95. [DOI] [PubMed] [Google Scholar]
  28. Van Voorhis W.C., Steinman R.M., Hair L.S., Luban J., Witmer M.D., Koide S., Cohn J.A. Specific antimononuclear phagocyte monoclonal antibodies: Application to the purification of dendritic cells and the tissue localization of macrophages. J. Exp. Med. 1983;158:126–145. doi: 10.1084/jem.158.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wallace L.E., Wright J., Ulaeto D.O., Morgan A.J., Rickinson A.B. Identification of two T-cell epitopes on the candidate Epstein-Barr virus vaccine glycoprotein gp340 recognized by CD4+ T-cell clones. J. Virol. 1991;65:3821–3828. doi: 10.1128/jvi.65.7.3821-3828.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Virology are provided here courtesy of Elsevier

RESOURCES