Abstract
IMMUNOGLOBULIN and T-cell receptor (TCR) molecules are central to the adaptive immune system. Sequence conservation, similarities in domain structure, and usage of similar recombination signal sequences and recombination machinery indicate that there was probably a time during evolution when an ancestral receptor diverged to the modern-day immunoglobulin and TCR1–3. Other molecules that undergo rearrangement have not been described in vertebrates, nor have intermediates been identified that have features of both these gene families. We report here the isolation of a new member of the immunoglobulin superfamily from the nurse shark, Ginglymostoma cirratum, which contains one variable and five constant domains and is found as a dimer in serum. Analyses of complementary DNA clones show extensive sequence diversity within variable domains, which is generated by both rearrangement and somatic diversification mechanisms. Our results suggest that rearranging loci distinct from immunoglobulin and TCR have arisen during evolution.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hedrick, S. M., Nilsen, E. A., Kavaler, J., Cohen, D. I. & Davis, M. M. Nature 308, 153–158 (1984).
Yancopoulos, G. D., Blackwell, T. K., Suh, H. Hood, L. & Alt, F. W. Cell 44, 251–259 (1986).
Davis, M. M. & Bjorkman, P. J. Nature 334, 395–402 (1988).
Greenberg, A. S., Steiner, L., Kasahara, M. & Flajnik, M. F. Proc. natn. Acad. Sci. U.S.A. 90, 10603–10607 (1993).
Frohman, M. A., Dush, M. K. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).
Williams, A. F. & Barclay, A. N. A. Rev. Immun. 6, 381–405 (1988).
Chothia, C., Boswell, D. R. & Lesk, A. M. EMBO J. 7, 3745–3755 (1988).
Staudt, L. M. & Lenardo, M. F. A. Rev. Immun. 9, 373–398 (1991).
Clem, L. W. & Leslie, G. A. Proc. natn. Acad. Sci. U.S.A. 68, 139–141 (1971).
Mäkela, O. & Litman, G. W. Nature 287, 639–640 (1980).
Du Pasquier, L. in Fundamental Immunology 3rd edn (ed. Paul, W. E.) 199–233 (Raven, New York, 1993).
Smith, L. C. & Davidson, E. H. Ann. N. Y. Acad. Sci. 712, 213–226 (1994).
Reynaud, C.-A., Mackay, C. R., Müller, R. G. & Weill, J.-C. Cell 64, 995–1005 (1991).
Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M. & Grottesman, K. S. Sequences of Proteins Immunological Interest (US Department of Health and Human Services, NIH, Washington DC, 1991).
Saitou, N. & Nei, M. Molec. Biol. Evol. 4, 406–425 (1987).
Rzhetsky, A. & Nei, H. Molec. Biol. Evol. 9, 945–967 (1992).
Southern, E. J. molec. Biol. 98, 503–517 (1975).
Kearney, J. F., Radbruch, A., Liesegang, B. & Rajewsky, K. J. Immun. 123, 1548–1550 (1979).
Flajnik, M. F., Taylor, E., Canel, C., Grossberger, D. & Du Pasquier, L. Amer. Zool. 31, 580–591 (1991).
Hsu, E. & Du Pasquier, L. Molec. Immun. 21, 257–270 (1984).
Tamura, G. S. et al. Analyt. Biochem. 136, 458–464 (1984).
Laemmli, U. K. Nature 227, 680–685 (1970).
Schneider, C., Newman, R. A., Sutherland, D. R., Asser, U. & Greaves, M. F. J. biol. Chem. 257, 10766–10769 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Greenberg, A., Avila, D., Hughes, M. et al. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks. Nature 374, 168–173 (1995). https://doi.org/10.1038/374168a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/374168a0
This article is cited by
-
Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy
Cell Death & Disease (2024)
-
Screening of nanobody targeting alkaline phosphatase PhoX in Microcystis and detection of the PhoX in situ by fluorescence immunoassays
Journal of Applied Phycology (2023)
-
Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity
Nature Communications (2023)
-
Marine-derived microbes and molecules for drug discovery
Inflammation and Regeneration (2022)
-
The journey of CAR-T therapy in hematological malignancies
Molecular Cancer (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
