Abstract

The Major Histocompatibility Complex (MHC) encodes molecules that provide a context for the recognition of antigen by T lymphocytes. Because of its central role in individuals' immune response, the MHC has been studied extensively by immunologists and geneticists. However, the information concerning its evolution is scant and largely limited to primates and a few rodent species. The overall goal of the proposed project is to study the MHCs of lower vertebrates by molecular cloning.
The specific aims of this proposal are threefold: First, the organization of the MHC of an African clawed frog Xenopus will be studied using a recently isolated class I cDNA clone as a starting material. Second, the regulation of MHC expression in ontogeny, in particular, in metamorphosis, will be studied in various amphibian species including Xenopus and axolotl. And third, using Xenopus as a stepping stone, the MHC genes of more primitive species (shark, lamprey, and tunicates) will be isolated. Xenopus is clearly a """"""""high connectivity"""""""" model. The information obtained from this study should further enhance its connectivity as a model organism for biomedical research. In terms of immunology, the isolation and characterization of MHC genes from primitive species should provide a clue to the primordial function of the MHC, and increase our knowledge about the evolution of immunity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR006603-04
Application #
2283253
Study Section
Special Emphasis Panel (SRC (BM))
Project Start
1991-02-11
Project End
1995-07-31
Budget Start
1994-02-11
Budget End
1995-07-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Miami School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146

  Publications

Redmond, Anthony K; Ohta, Yuko; Criscitiello, Michael F et al. (2018) Haptoglobin Is a Divergent MASP Family Member That Neofunctionalized To Recycle Hemoglobin via CD163 in Mammals. J Immunol 201:2483-2491
Neely, Harold R; Flajnik, Martin F (2015) CXCL13 responsiveness but not CXCR5 expression by late transitional B cells initiates splenic white pulp formation. J Immunol 194:2616-23
Venkatesh, Byrappa; Lee, Alison P; Ravi, Vydianathan et al. (2014) Elephant shark genome provides unique insights into gnathostome evolution. Nature 505:174-9
Castro, Caitlin D; Ohta, Yuko; Dooley, Helen et al. (2013) Noncoordinate expression of J-chain and Blimp-1 define nurse shark plasma cell populations during ontogeny. Eur J Immunol 43:3061-75
Smith, Lauren E; Crouch, Kathryn; Cao, Wei et al. (2012) Characterization of the immunoglobulin repertoire of the spiny dogfish (Squalus acanthias). Dev Comp Immunol 36:665-79
Flajnik, Martin F; Tlapakova, Tereza; Criscitiello, Michael F et al. (2012) Evolution of the B7 family: co-evolution of B7H6 and NKp30, identification of a new B7 family member, B7H7, and of B7's historical relationship with the MHC. Immunogenetics 64:571-90
Criscitiello, Michael F; Ohta, Yuko; Saltis, Mark et al. (2010) Evolutionarily conserved TCR binding sites, identification of T cells in primary lymphoid tissues, and surprising trans-rearrangements in nurse shark. J Immunol 184:6950-60
Flajnik, Martin F (2010) All GOD's creatures got dedicated mucosal immunity. Nat Immunol 11:777-9
Flajnik, Martin F; Kasahara, Masanori (2010) Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat Rev Genet 11:47-59
Dooley, Helen; Buckingham, E Bryan; Criscitiello, Michael F et al. (2010) Emergence of the acute-phase protein hemopexin in jawed vertebrates. Mol Immunol 48:147-52

Showing the most recent 10 out of 55 publications