Martin F. Flajnik, Ph.D.
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Postdoc.,
Basel Institute for Immunology, Basel, Switzerland, 1983-1988 Research InterestsMy work is centered on the evolution of the immune system, with the major goal being to understand the origins of adaptive immunity. The laboratory employs a “holistic” approach, using all existing methods to investigate this problem. The adaptive immune system is defined by antigen receptors of great diversity immunoglobulin (Ig) and T cell receptors (TCR) and by molecules encoded in the major histocompatibility complex (MHC) that present foreign antigens for T cell recognition. In addition, the adaptive immune system is contrasted to the non-adaptive or innate immune system by displaying: i) great diversity of the antigen-receptor repertoire; ii) specific and augmented memory responses; and iii) epigenetically determined self tolerance. We believe that evolutionary studies permit a judgment of those structures and mechanisms vital for a functioning immune system and reveal other phenomena that have arisen to fulfill specific functions in particular taxonomic lineages. The adaptive immune system so far has been identified only in jawed vertebrates, including the cartilaginous fish (e.g. sharks and skates), bony fish (e.g. trout, zebrafish), amphibians (e.g. Xenopus), reptiles, birds, and mammals. Our work (and that of other labs) has shown that the oldest group, the cartilaginous fish, while exhibiting an unusual immune system in which specific antibody responses do not increase in quality over time, nevertheless possess all of the building blocks of an adaptive immune system. We hope to build on these studies to identify related genes/mechanisms in more ancient groups of organisms that do not possess a true adaptive immune system. Research Publications Flajnik MF, Du Pasquier L. Evolution of
innate and adaptive immunity: can we draw a line? Trends Immunol. 2004
Dec;25(12):640-4. Ohta Y, Landis E, Boulay T, Phillips RB, Collet B, Secombes CJ, Flajnik MF, Hansen JD. Homologs of CD83 from elasmobranch and teleost fish.J Immunol. 2004 Oct 1;173(7):4553-60. Stanfield RL, Dooley H, Flajnik MF, Wilson IA. Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Science. 2004 Sep 17;305(5691):1770-3. Rumfelt LL, Diaz M, Lohr RL, Mochon E, Flajnik MF. Unprecedented multiplicity of Ig transmembrane and secretory mRNA forms in the cartilaginous fish. J Immunol. 2004 Jul 15;173(2):1129-39. Flajnik MF. Immunology: another manifestation of GOD. Nature. 2004 Jul 8;430(6996):157-8. Rumfelt LL, Lohr RL, Dooley H, Flajnik MF. Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark. BMC Immunol. 2004 May 06;5(1):8. Bartl S, Miracle AL, Rumfelt LL, Kepler TB, Mochon E, Litman GW, Flajnik MF. Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural conservation within vertebrates. Immunogenetics. 2003 Dec;55(9):594-604. Ohta Y, Powis SJ, Lohr RL, Nonaka M, Pasquier LD, Flajnik MF. Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co-evolution among MHC class I region genes. Eur J Immunol. 2003 Nov;33(11):3017-27. Terado T, Okamura K, Ohta Y, Shin DH, Smith SL, Hashimoto K, Takemoto T, Nonaka MI, Kimura H, Flajnik MF, Nonaka M. Molecular cloning of C4 gene and identification of the class III complement region in the shark MHC. J Immunol. 2003 Sep 1;171(5):2461-6. Dooley H, Flajnik MF, Porter AJ. Selection and characterization of naturally occurring single-domain (IgNAR) antibody fragments from immunized sharks by phage display. Mol Immunol. 2003 Sep;40(1):25-33. Hohman VS, Stewart SE, Rumfelt LL, Greenberg AS, Avila DW, Flajnik MF,Steiner LA. J chain in the nurse shark: implications for function in a lower vertebrate. J Immunol. 2003 Jun 15;170(12):6016-23. Liu Y, Kasahara M, Rumfelt LL, Flajnik MF. Xenopus class II A genes: studies of genetics, polymorphism, and expression. Dev Comp Immunol. 2002 Oct;26(8):735-50. Ohta, Y., McKinney, E.C., Criscitiello, M.F., and Flajnik, M.F. 2002. Proteasome, TAP, and class I genes in the nurse shark Ginglymostoma cirratum: Evidence for a stable class I region and MHC haplotype lineages. J. Immunol. 168:771-781. Flajnik, M.F. and Kasahara, M. 2001. Comparative genomics of the MHC: Glimpses into the evolution of the adaptive immune system. Immunity 15:351-362. Rumfelt, L.L., Avila, D., Diaz, M., McKinney, E.C., and Flajnik, M.F. 2001. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG. Proc. Natl. Acad. Sci. 98:1775-1780. Lee, S.S., Fitch, D., Flajnik, M.F., and Hsu, E. 2000. Rearrangement of immunoglobulin genes in shark germ cells. J. Exp. Med. 191:1637-1648. Ohta, Y., Okamura, K., McKinney, E.C., Bartl, S., Hashimoto, K., and Flajnik, M.F. 2000. Primitive synteny of vertebrate major histocompatibility complex class I and class II genes. Proc. Natl. Acad. Sci. 97:4712-4717. Flajnik, M.F. 2002. Comparative analysis of immunoglobulin genes: surprises and portents. Nature Reviews Immunology 2:688-698 |
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