Thymic selection and adaptability of cytotoxic T lymphocyte responses in transgenic mice expressing a viral protein in the thymus - PubMed (original) (raw)
Thymic selection and adaptability of cytotoxic T lymphocyte responses in transgenic mice expressing a viral protein in the thymus
M G von Herrath et al. J Exp Med. 1994.
Abstract
Upon primary challenge with lymphocytic choriomeningitis virus (LCMV), H-2d (BALB/cByJ) mice mount a cytotoxic T lymphocyte (CTL) response to a single immunodominant domain of the viral nucleoprotein (NP) but no detectable response to the viral glycoprotein (GP). To manipulate this CTL response, the viral NP gene was expressed in the thymus and peripheral T lymphocytes using the murine Thy1.2 promoter. As a result, such Thy1.2-NP (H-2d) transgenic (tg) mice deleted their high-affinity anti-LCMV-NP CTL, but generated equal numbers of lower-affinity NP CTL. Further, they made an alternative anti-LCMV-GP CTL response that is not normally found in non-tg mice indicating a hierarchial control of the CTL response. Unlike the H-2d mice, H-2b (C57Bl/6J) mice normally mount a CTL response to both LCMV-GP and -NP. When the LCMV-NP was expressed using the Thy1.2 promoter in these H-2b mice, the LCMV-NP-specific CTL response was completely aborted and no CTL to new, alternative viral epitopes were generated. Dilutions of H-2b or H-2d NP peptides indicated that 3-4 logs less H-2b NP peptide was required to sensitize syngeneic target cells for CTL-specific lysis, suggesting that the differing affinities of H-2b and H-2d major histocompatibility complex molecules for their peptides likely account for the total removal of NP CTL in the H-2b mice but only partial removal in H-2d mice made to express thymic NP. Thymic grafting experiments done with thymi from newborn Thy1.2-NP tg mice show that selection processes studied in this model are of central (thymic) origin and are not caused by Thy1.2-positive LCMV-NP-expressing T lymphocytes in the periphery.
Similar articles
- Immunological tolerance to LCMV antigens differently affects control of acute and chronic virus infection in mice.
Woopen C, Straub T, Schweier O, Aichele U, Düker K, Boehm T, Pircher H. Woopen C, et al. Eur J Immunol. 2018 Jan;48(1):120-127. doi: 10.1002/eji.201747156. Epub 2017 Sep 15. Eur J Immunol. 2018. PMID: 28921501 - Low-affinity cytotoxic T-lymphocytes require IFN-gamma to clear an acute viral infection.
Von Herrath MG, Coon B, Oldstone MB. Von Herrath MG, et al. Virology. 1997 Mar 17;229(2):349-59. doi: 10.1006/viro.1997.8442. Virology. 1997. PMID: 9126248 - Hierarchies of antigen-specific cytotoxic T-cell responses.
Gallimore A, Hengartner H, Zinkernagel R. Gallimore A, et al. Immunol Rev. 1998 Aug;164:29-36. doi: 10.1111/j.1600-065x.1998.tb01205.x. Immunol Rev. 1998. PMID: 9795761 Review.
Cited by
- Autoallergy in atopic dermatitis.
Hradetzky S, Werfel T, Rösner LM. Hradetzky S, et al. Allergo J Int. 2015;24(1):16-22. doi: 10.1007/s40629-015-0037-5. Epub 2015 Feb 9. Allergo J Int. 2015. PMID: 26120543 Free PMC article. Review. - The rationale of vectored gene-fusion vaccines against cancer: evolving strategies and latest evidence.
Ragonnaud E, Holst P. Ragonnaud E, et al. Ther Adv Vaccines. 2013 May;1(1):33-47. doi: 10.1177/2051013613480446. Ther Adv Vaccines. 2013. PMID: 24757514 Free PMC article. - Molecular anatomy and number of antigen specific CD8 T cells required to cause type 1 diabetes.
Oldstone MB, Edelmann KH, McGavern DB, Cruite JT, Welch MJ. Oldstone MB, et al. PLoS Pathog. 2012;8(11):e1003044. doi: 10.1371/journal.ppat.1003044. Epub 2012 Nov 29. PLoS Pathog. 2012. PMID: 23209415 Free PMC article. - Memory CD8+ T cells specific for a single immunodominant or subdominant determinant induced by peptide-dendritic cell immunization protect from an acute lethal viral disease.
Remakus S, Rubio D, Ma X, Sette A, Sigal LJ. Remakus S, et al. J Virol. 2012 Sep;86(18):9748-59. doi: 10.1128/JVI.00981-12. Epub 2012 Jun 27. J Virol. 2012. PMID: 22740418 Free PMC article. - Protective efficacy of serially up-ranked subdominant CD8+ T cell epitopes against virus challenges.
Im EJ, Hong JP, Roshorm Y, Bridgeman A, Létourneau S, Liljeström P, Potash MJ, Volsky DJ, McMichael AJ, Hanke T. Im EJ, et al. PLoS Pathog. 2011 May;7(5):e1002041. doi: 10.1371/journal.ppat.1002041. Epub 2011 May 19. PLoS Pathog. 2011. PMID: 21625575 Free PMC article.
References
- J Exp Med. 1978 Aug 1;148(2):534-43 - PubMed
- Immunity. 1994 Jun;1(3):231-42 - PubMed
- Adv Immunol. 1980;30:275-331 - PubMed
- Virology. 1981 Aug;113(1):73-85 - PubMed
- J Gen Virol. 1983 Aug;64 (Pt 8):1689-98 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous