Skip to main content
SpringerLink
Log in

Immunoglobulin variable regions in molecules exhibiting characteristics of innate and adaptive immune receptors

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

The antigen combining sites of immunoglobulin (Ig) and T cell antigen receptors (TCRs), which are present in all jawed vertebrates, consist of a paired variable (V) domain heterodimer that exhibits varying degrees of germline- and extraordinarily high levels of somatically-derived variation. The near limitless variation in receptor specificity on the surface of individual lymphocytes is the basis for clonal selection in the adaptive immune response. A basic question arises as to whether or not there are other forms of immune-type receptors in vertebrates as well as in invertebrates that derive immune specificity through sequence differences in V domains. Our laboratory has discovered two such families of molecules, the novel immune-type receptors and the variable region-containing chitin-binding proteins. Both families of molecules encode V domains that share some characteristics of adaptive immune receptors but likely mediate innate functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Chothia C, Gelfand I, Kister A. Structural determinants in the sequences of immunoglobulin variable domains. J Mol Biol 1998;278;457–79

    Article  PubMed  CAS  Google Scholar 

  2. Bork P, Holm L, Sander C. The immunoglobulin fold. Structural classification, sequence patterns and common core. J Mol Biol 1994;242:309–20

    PubMed  CAS  Google Scholar 

  3. Garrett TP, Wang J, Yan Y, Liu J, Harrison SC. Refinement and analysis of the structure of the first two domains of human CD4. J Mol Biol 1993;234:763–78

    Article  PubMed  CAS  Google Scholar 

  4. Leahy DJ, Axel R, Hendrickson WA. Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 Å resolution. Cell 1992;68:1145–62

    Article  PubMed  CAS  Google Scholar 

  5. Cantoni C, Ponassi M, Biassoni R, et al. The three-dimensional structure of the human NK cell receptor NKp44, a triggering partner in natural cytotoxicity. Structure (Camb) 2003;11:725–34

    Article  CAS  Google Scholar 

  6. Suzuki T, Shin I, Fujiyama A, Kohara Y, Kasahara M. Hagfish leukocytes express a paired receptor family with a variable domain resembling those of antigen receptors. J Immunol 2005;174:2885–91

    PubMed  CAS  Google Scholar 

  7. Haruta C, Suzuki T, Kasahara M. Variable domains in hagfish: NICIR is a polymorphic multigene family expressed preferentially in leukocytes and is related to lamprey TCR-like. Immunogenet 2006;58:216–25

    Article  CAS  Google Scholar 

  8. Rast JP, Anderson MK, Strong SJ, Luer C, Litman RT, Litman GW. α, β, γ, and δ T cell antigen receptor genes arose early in vertebrate phylogeny. Immunity 1997;6:1–11

    Article  PubMed  CAS  Google Scholar 

  9. Rast JP, Haire RN, Litman RT, Pross S, Litman GW. Identification and characterization of T-cell antigen receptor related genes in phylogenetically diverse vertebrate species. Immunogenet 1995;42:204–12

    Article  CAS  Google Scholar 

  10. Strong SJ, Mueller MG, Litman RT, et al. A novel multigene family encodes diversified variable regions. Proc Natl Acad Sci USA 1999;96:15080–5

    Article  PubMed  CAS  Google Scholar 

  11. Traver T, Herbomel P, Patton EE, et al. The zebrafish as a model organism to study development of the immune system. Adv Immunol 2003;81:253–330

    PubMed  Google Scholar 

  12. Yoder JA, Mueller MG, Wei S, et al. Immune-type receptor genes in zebrafish share genetic and functional properties with genes encoded by the mammalian lymphocyte receptor cluster. Proc Natl Acad Sci USA 2001;98:6771–6

    Article  PubMed  CAS  Google Scholar 

  13. Hawke NA, Yoder JA, Haire RN, et al. Extraordinary variation in a diversified family of immune-type receptor genes. Proc Natl Acad Sci USA 2001;98:13832–7

    Article  PubMed  CAS  Google Scholar 

  14. Yoder JA, Litman RT, Mueller MG, et al. Resolution of the NITR gene cluster in zebrafish. Proc Natl Acad Sci USA 2004;101:15706–11

    Article  PubMed  CAS  Google Scholar 

  15. Sidorenko SP, Clark EA. The dual-function CD150 receptor subfamily: the viral attraction. Nat Immunol 2003;4:19–24

    Article  PubMed  CAS  Google Scholar 

  16. Dietrich J, Nakajima H, Colonna M. Human inhibitory and activating Ig-like receptors which modulate the function of myeloid cells. Microbes Infect 2000;2:323–9

    Article  PubMed  CAS  Google Scholar 

  17. Ota T, Nei M. Divergent evolution and evolution by the birth-and-death process in the immunoglobulin VH gene family. Mol Biol Evol 1994;11:469–82

    PubMed  CAS  Google Scholar 

  18. Vilches C, Parham P. KIR: Diverse, rapidly evolving receptors of innate and adaptive immunity. Ann Rev Immunol 2002;20:217–51

    Article  CAS  Google Scholar 

  19. Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 2005;5:201–14

    Article  PubMed  CAS  Google Scholar 

  20. Litman GW, Hawke NA, Yoder JA. Novel immune-type receptor genes. Immunol Rev 2001;181:250–9

    Article  PubMed  CAS  Google Scholar 

  21. Shen L, Stuge TB, Bengten E, et al. Identification and characterization of clonal NK-like cells from channel catfish. Ictalurus punctatus). Dev Comp Immunol 2004;28:139–52

    Article  PubMed  CAS  Google Scholar 

  22. Cantoni C, Bottino C, Vitale A, et al. NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily. J Exp Med 1999;189:787

    Article  PubMed  CAS  Google Scholar 

  23. Pende D, Parolini S, Pessino A, et al. Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med 1999;190:1505–16

    Article  PubMed  CAS  Google Scholar 

  24. Pancer Z, Amemiya CT, Ehrhardt RA, Ceitlin J, Gartland GL, Cooper MD. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 2004;430:174–80

    Article  PubMed  CAS  Google Scholar 

  25. Alder MN, Rogozin IB, Iyer LM, Glazko GV, Cooper MD, Pancer Z. Diversity and function of adaptive immune receptors in a jawless vertebrate. Science 2005;310:1970–3

    Article  PubMed  CAS  Google Scholar 

  26. Cannon JP, Haire RN, Pancer Z, et al. Variable domains and a VpreB-like molecule are present in a jawless vertebrate. Immunogenet 2005;56:924–9

    Article  CAS  Google Scholar 

  27. Melchers F, ten Boekel E, Seidl T, et al. Repertoire selection by pre-B-cell receptors and B-cell receptors, and genetic control of B-cell development from immature to mature B cells. Immunol Rev 2000;175:33–46

    Article  PubMed  CAS  Google Scholar 

  28. Kusserow A, Pang K, Sturm C, et al. Unexpected complexity of the Wnt gene family in a sea anemone. Nature 2005;433:156–60

    Article  PubMed  CAS  Google Scholar 

  29. Cannon JP, Haire RN, Litman GW. Identification of diversified genes that contain immunoglobulin-like variable regions in a protochordate. Nat Immunol 2002;3:1200–7

    Article  PubMed  CAS  Google Scholar 

  30. Litman GW, Cannon JP, Dishaw LJ. Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol 2005;5:866–79

    Article  PubMed  CAS  Google Scholar 

  31. Cannon JP, Haire RN, Schnitker N, Mueller MG, Litman GW. Individual protochordates possess unique immune-type receptor repertoires. Curr Biol 2004;14:R465–6

    Article  PubMed  CAS  Google Scholar 

  32. Hernandez Prada JA, Haire RN, Allaire M, et al. Ancient evolutionary origin of diversified variable regions revealed by crystal structures of an amphioxus VCBP. Nat Immunol 2006;7:875–82

    Article  PubMed  CAS  Google Scholar 

  33. Chothia C, Novotny J, Bruccoleri R, Karplus M. Domain association in immunoglobulin molecules. The packing of variable domains. J Mol Biol 1985;186:651–63

    Article  PubMed  CAS  Google Scholar 

  34. Cannon JP, Haire RN, Rast JP, Litman GW. The phylogenetic origins of the antigen binding receptors and somatic diversification mechanisms. Immunol Rev 2004;200:12–22

    Article  PubMed  CAS  Google Scholar 

  35. Fedtke I, Gotz F, Peschel A. Bacterial evasion of innate host defenses—the Staphylococcus aureus lesson. Int J Med Microbiol 2004;294:189–94

    Article  PubMed  CAS  Google Scholar 

  36. Roberts ME, Stewart PS. Modelling protection from antimicrobial agents in biofilms through the formation of persister cells. Microbiology 2005;151:75–80

    Article  PubMed  CAS  Google Scholar 

  37. Sutherland IW. The biofilm matrix—an immobilized but dynamic microbial environment. Trends Microbiol 2001;9:222–7

    Article  PubMed  CAS  Google Scholar 

  38. Kwiatkowski DP. The complexity of genetic variation in a simple immune system. Trends Genet 2005;21:197–9

    Article  PubMed  CAS  Google Scholar 

  39. Lazzaro BP, Sceurman BK, Clark AG. Genetic basis of natural variation in D. melanogaster antibacterial immunity. Science 2004;303:1873–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank B. Pryor for editorial assistance. This work is supported by National Institutes of Health (R01 AI23338 and AI 57559 to GWL; R01 DE013883 and R21 HL080222 to DAO), Cure Autism Now Foundation (2908051-12 to DAO), The Pediatric Cancer Foundation (to GWL), All Children’s Hospital Foundation (to GWL), H. Lee Moffitt Cancer Center and Research Institute (postdoctoral fellowship to LJD), and National Science Foundation (MCB-0505585 to JAY).

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of South Florida College of Medicine, USF/ACH Children’s Research Institute, 830 First Street South, St. Petersburg, FL, 33701, USA

    Gary W. Litman, John P. Cannon, Robert N. Haire & Donna D. Eason

  2. Department of Molecular Genetics, All Children’s Hospital, 801 Sixth Street South, St. Petersburg, FL, 33701, USA

    Gary W. Litman & Larry J. Dishaw

  3. H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Avenue, Tampa, FL, 33612, USA

    Gary W. Litman, John P. Cannon, Larry J. Dishaw, Robert N. Haire & Donna D. Eason

  4. Department of Molecular Biomedical Sciences, College of Veterinary Medicine North Carolina State University, 4700 Hillsborough Street, Raleigh, NC, 27606, USA

    Jeffrey A. Yoder

  5. Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL, 32610, USA

    Jose Hernandez Prada & David A. Ostrov

Authors
  1. Gary W. Litman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John P. Cannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Larry J. Dishaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert N. Haire
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Donna D. Eason
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeffrey A. Yoder
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jose Hernandez Prada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David A. Ostrov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary W. Litman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Litman, G.W., Cannon, J.P., Dishaw, L.J. et al. Immunoglobulin variable regions in molecules exhibiting characteristics of innate and adaptive immune receptors. Immunol Res 38, 294–304 (2007). https://doi.org/10.1007/s12026-007-0014-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-007-0014-2

Keywords

Search

Navigation