From Immunity and Vaccines to Mammalian Regeneration

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2015 Jun 28

PMID 26116734

Authors

Ellen Heber-Katz

Affiliations

Soon will be listed here.

Abstract

Our current understanding of major histocompatibility complex (MHC)-mediated antigen presentation in self and nonself immune recognition was derived from immunological studies of autoimmunity and virus-host interactions, respectively. The trimolecular complex of the MHC molecule, antigen, and T-cell receptor accounts for the phenomena of immunodominance and MHC degeneracy in both types of responses and constrains vaccine development. Out of such considerations, we developed a simple peptide vaccine construct that obviates immunodominance, resulting in a broadly protective T-cell response in the absence of antibody. In the course of autoimmunity studies, we identified the MRL mouse strain as a mammalian model of amphibian-like regeneration. A significant level of DNA damage in the cells from this mouse pointed to the role of the cell cycle checkpoint gene CDKN1a, or p21(cip1/waf1). The MRL mouse has highly reduced levels of this molecule, and a genetic knockout of this single gene in otherwise nonregenerating strains led to an MRL-type regenerative response, indicating that the ability to regenerate has not been lost during evolution.

References

Desquenne-Clark L, Esch T, Otvos Jr L, Heber-Katz E . T-cell receptor peptide immunization leads to enhanced and chronic experimental allergic encephalomyelitis. Proc Natl Acad Sci U S A. 1991; 88(16):7219-23. PMC: 52265. DOI: 10.1073/pnas.88.16.7219. View

Cheverud J, Lawson H, Bouckaert K, Kossenkov A, Showe L, Cort L . Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line. Heredity (Edinb). 2014; 112(5):508-18. PMC: 3998788. DOI: 10.1038/hdy.2013.133. View

Bedelbaeva K, Gourevitch D, Clark L, Chen P, Leferovich J, Heber-Katz E . The MRL mouse heart healing response shows donor dominance in allogeneic fetal liver chimeric mice. Cloning Stem Cells. 2005; 6(4):352-63. DOI: 10.1089/clo.2004.6.352. View

Heber-Katz E, Schwartz R, Matis L, Hannum C, Fairwell T, Appella E . Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation. J Exp Med. 1982; 155(4):1086-99. PMC: 2186641. DOI: 10.1084/jem.155.4.1086. View

Leferovich J, Bedelbaeva K, Samulewicz S, Zhang X, Zwas D, Lankford E . Heart regeneration in adult MRL mice. Proc Natl Acad Sci U S A. 2001; 98(17):9830-5. PMC: 55538. DOI: 10.1073/pnas.181329398. View

Hansburg D, Heber-Katz E, Fairwell T, Appella E . Major histocompatibility complex-controlled, antigen-presenting cell-expressed specificity of T cell antigen recognition. Identification of a site of interaction and its relationship to Ir genes. J Exp Med. 1983; 158(1):25-39. PMC: 2187065. DOI: 10.1084/jem.158.1.25. View

Heber-Katz E, Hansburg D, Schwartz R . The effect of antigen presentation on the fine specificity of anti-cytochrome c T cell hybridomas. Curr Top Microbiol Immunol. 1982; 100:117-24. DOI: 10.1007/978-3-642-68586-6_14. View

Heber-Katz E, Zhang Y, Bedelbaeva K, Song F, Chen X, Stocum D . Cell cycle regulation and regeneration. Curr Top Microbiol Immunol. 2012; 367:253-76. DOI: 10.1007/82_2012_294. View

Mordes J, Cort L, Norowski E, Leif J, Fuller J, Lernmark A . Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V locus. Mamm Genome. 2009; 20(3):162-9. PMC: 3962255. DOI: 10.1007/s00335-009-9172-y. View

10.

Heber-Katz E, Leferovich J, Bedelbaeva K, Gourevitch D, Clark L . The scarless heart and the MRL mouse. Philos Trans R Soc Lond B Biol Sci. 2004; 359(1445):785-93. PMC: 1693365. DOI: 10.1098/rstb.2004.1468. View

11.

Arthur L, Demarest R, Clark L, Gourevitch D, Bedelbaeva K, Anderson R . Epimorphic regeneration in mice is p53-independent. Cell Cycle. 2010; 9(18):3667-73. PMC: 3047795. DOI: 10.4161/cc.9.18.13119. View

12.

Seitz A, Kragol M, Aglow E, Showe L, Heber-Katz E . Apolipoprotein E expression after spinal cord injury in the mouse. J Neurosci Res. 2003; 71(3):417-26. DOI: 10.1002/jnr.10482. View

13.

Lider O, Miller A, MIRON S, Hershkoviz R, Weiner H, Zhang X . Nonencephalitogenic CD4-CD8- V alpha 2V beta 8.2+ anti-myelin basic protein rat T lymphocytes inhibit disease induction. J Immunol. 1991; 147(4):1208-13. View

14.

Gregerson D, Fling S, Merryman C, Zhang X, Li X, Heber-Katz E . Conserved T cell receptor V gene usage by uveitogenic T cells. Clin Immunol Immunopathol. 1991; 58(1):154-61. DOI: 10.1016/0090-1229(91)90157-6. View

15.

Gourevitch D, Clark L, Chen P, Seitz A, Samulewicz S, Heber-Katz E . Matrix metalloproteinase activity correlates with blastema formation in the regenerating MRL mouse ear hole model. Dev Dyn. 2003; 226(2):377-87. DOI: 10.1002/dvdy.10243. View

16.

Lee J, Kim J, Barbier V, Fotedar A, Fotedar R . DNA damage triggers p21WAF1-dependent Emi1 down-regulation that maintains G2 arrest. Mol Biol Cell. 2009; 20(7):1891-902. PMC: 2663934. DOI: 10.1091/mbc.e08-08-0818. View

17.

Seitz A, Gourevitch D, Zhang X, Clark L, Chen P, Kragol M . Sense and antisense transcripts of the apolipoprotein E gene in normal and ApoE knockout mice, their expression after spinal cord injury and corresponding human transcripts. Hum Mol Genet. 2005; 14(18):2661-70. DOI: 10.1093/hmg/ddi296. View

18.

McBrearty B, CLARK L, Zhang X, Blankenhorn E, Heber-Katz E . Genetic analysis of a mammalian wound-healing trait. Proc Natl Acad Sci U S A. 1998; 95(20):11792-7. PMC: 21719. DOI: 10.1073/pnas.95.20.11792. View

19.

Hampton D, Seitz A, Chen P, Heber-Katz E, Fawcett J . Altered CNS response to injury in the MRL/MpJ mouse. Neuroscience. 2004; 127(4):821-32. DOI: 10.1016/j.neuroscience.2004.05.057. View

20.

Heber-Katz E . A new hierarchy of TCR specificity: autoimmune diseases are defined by particular V alpha V beta combinations and not by antigen specificity. Cold Spring Harb Symp Quant Biol. 1989; 54 Pt 2:875-8. DOI: 10.1101/sqb.1989.054.01.101. View