title: From Immunity and Vaccines to Mammalian Regeneration.
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.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania.
authors.forename: Ellen
authors.initials: E
authors.lastname: Heber-Katz
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004423:Ear / Q000293:injuries / Q000473:pathology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012038:Regeneration / Q000235:genetics* / Q000276:immunology*; D012867:Skin / Q000293:injuries / Q000473:pathology; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D011948:Receptors, Antigen, T-Cell; D022223:Vaccines, Subunit
keywords: CDKN1a; HSV gD; MRL mouse; comets; immunodominance; mammalian regeneration; p21cip1/waf1; peptide-palmitic acid; trimolecular complex; vaccine