Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Co-evolution of a primordial peptide-presentation system and cellular immunity

Abstract

How did early vertebrates survive when their lymphocytes began to use antigen receptors with random specificities, despite their potential for extensive self-reactivity? Here, I propose that the quality-control mechanisms that tame self-reactivity in the adaptive immune system were derived, at least in part, from an ancient mechanism that guided sexual selection on the basis of evaluating genetic relatedness.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Features of intercellular discrimination based on intracellular components.
Figure 2: Structural information embedded in ligand–carrier pairs.
Figure 3: Evolution of intercellular from inter-individual discrimination.

References

  1. Medzhitov, R. & Janeway, C. A. Jr. Decoding the patterns of self and nonself by the innate immune system. Science 296, 298–300 (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Lanier, L. L. NK cell recognition. Annu. Rev. Immunol. 23, 225–274 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Pancer, Z. et al. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 430, 174–180 (2004).

    CAS  PubMed  Google Scholar 

  4. Pancer, Z. et al. Variable lymphocyte receptors in hagfish. Proc. Natl Acad. Sci. USA 102, 9224–9229 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tonegawa, S. Somatic generation of antibody diversity. Nature 302, 575–581 (1983).

    CAS  PubMed  Google Scholar 

  6. Dudley, D. D., Chaudhuri, J., Bassing, C. H. & Alt, F. W. Mechanism and control of V(D)J recombination versus class switch recombination: similarities and differences. Adv. Immunol. 86, 43–112 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Sakano, H., Huppi, K., Heinrich, G. & Tonegawa, S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature 280, 288–294 (1979).

    Article  CAS  PubMed  Google Scholar 

  8. Agrawal, A., Eastman, Q. M. & Schatz, D. G. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 394, 744–751 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Hiom, K., Melek, M. & Gellert, M. DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations. Cell 94, 463–470 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Kapitonov, V. V. & Jurka, J. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biol. 3, e181 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Landsteiner, K. & van der Scheer, J. Serological differentiation of steric isomers. J. Exp. Med. 48, 315–320 (1928).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Allen, P. M. et al. Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope. Nature 327, 713–715 (1987).

    Article  CAS  PubMed  Google Scholar 

  13. Eason, D. D. et al. Mechanisms of antigen receptor evolution. Semin. Immunol. 16, 215–226 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Cannon, J. P., Haire, R. N., Rast, J. P. & Litman, G. W. The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms. Immunol. Rev. 200, 12–22 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Trombetta, E. S. & Mellman, I. Cell biology of antigen processing in vitro and in vivo. Annu. Rev. Immunol. 23, 975–1028 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Huseby, E. S. et al. How the T cell repertoire becomes peptide and MHC specific. Cell 122, 247–260 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Singer, A. & Bosselut, R. CD4/CD8 coreceptors in thymocyte development, selection, and lineage commitment: analysis of the CD4/CD8 lineage decision. Adv. Immunol. 83, 91–131 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Rudolph, M. G. & Wilson, I. A. The specificity of TCR/pMHC interaction. Curr. Opin. Immunol. 14, 52–65 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Hogquist, K. A., Baldwin, T. A. & Jameson, S. C. Central tolerance: learning self-control in the thymus. Nature Rev. Immunol. 5, 772–782 (2005).

    Article  CAS  Google Scholar 

  20. Rammensee, H. G., Bachmann, J. & Stefanovic, S. MHC Ligands and Peptide Motifs (Landes Bioscience, Georgetown, Texas, 1997).

    Book  Google Scholar 

  21. Falk, K., Rotzschke, O., Stevanovic, S., Jung, G. & Rammensee, H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351, 290–296 (1991).

    Article  CAS  PubMed  Google Scholar 

  22. Lopez de Castro, J. A. et al. HLA-B27: a registry of constitutive peptide ligands. Tissue Antigens 63, 424–445 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Bjorkman, P. J. & Parham, P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu. Rev. Biochem. 59, 253–288 (1990).

    Article  CAS  PubMed  Google Scholar 

  24. Madden, D. R., Gorga, J. C., Strominger, J. L. & Wiley, D. C. The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell 70, 1035–1048 (1992).

    Article  CAS  PubMed  Google Scholar 

  25. Penn, D. & Potts, W. How do major histocompatibility complex genes influence odour and mating preferences? Adv. Immunol. 69, 411–436 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Ziegler, A., Kentenich, H. & Uchanska-Ziegler, B. Female choice and the MHC. Trends Immunol. 26, 496–502 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Singh, P. B., Brown, R. E. & Roser, B. MHC antigens in urine as olfactory recognition cues. Nature 327, 161–164 (1987).

    Article  CAS  PubMed  Google Scholar 

  28. Leinders-Zufall, T. et al. MHC class I peptides as chemosensory signals in the vomeronasal organ. Science 306, 1033–1037 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Milinski, M. et al. Mate choice decisions of stickleback females predictably modified by MHC peptide ligands. Proc. Natl Acad. Sci. USA 102, 4414–4418 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bruce, H. M. An exteroceptive block to pregnancy in the mouse. Nature 184, 105 (1959).

    Article  CAS  PubMed  Google Scholar 

  31. Yamazaki, K. et al. Recognition of H-2 types in relation to the blocking of pregnancy in mice. Science 221, 186–188 (1983).

    Article  CAS  PubMed  Google Scholar 

  32. Brennan, P., Kaba, H. & Keverne, E. B. Olfactory recognition: a simple memory system. Science 250, 1223–1226 (1990).

    Article  CAS  PubMed  Google Scholar 

  33. Reusch, T. B., Haberli, M. A., Aeschlimann, P. B. & Milinski, M. Female sticklebacks count alleles in a strategy of sexual selection explaining MHC polymorphism. Nature 414, 300–302 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Brennan, P. A. & Keverne, E. B. Something in the air? New insights into mammalian pheromones. Curr. Biol. 14, R81–R89 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Mombaerts, P. Genes and ligands for odorant, vomeronasal and taste receptors. Nature Rev. Neurosci. 5, 263–278 (2004).

    Article  CAS  Google Scholar 

  36. Olson, R., Huey-Tubman, K. E., Dulac, C., Bjorkman, P. J. Structure of a pheromone receptor-associated MHC molecule with an open and empty groove. PLoS Biol. 3, e257 (2005).

  37. Brown, A. J. & Casselton, L. A. Mating in mushrooms: increasing the chances but prolonging the affair. Trends Genet. 17, 393–400 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Kronstad, J. W. & Staben, C. Mating type in filamentous fungi. Annu. Rev. Genet. 31, 245–276 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Ward, G. E., Brokaw, C. J., Garbers, D. L. & Vacquier, V. D. Chemotaxis of Arbacia punctulata spermatozoa to resact, a peptide from the egg jelly layer. J. Cell Biol. 101, 2324–2329 (1985).

    Article  CAS  PubMed  Google Scholar 

  40. Ram, J. L., Muller, C. T., Beckmann, M. & Hardege, J. D. The spawning pheromone cysteine-glutathione disulfide (“nereithione”) arouses a multicomponent nuptial behaviour and electrophysiological activity in Nereis succinea males. FASEB J. 13, 945–952 (1999).

    Article  CAS  PubMed  Google Scholar 

  41. Cummins, S. F., Schein, C. H., Xu, Y., Braun, W. & Nagle, G. T. Molluscan attractins, a family of water-borne protein pheromones with interspecific attractiveness. Peptides 26, 121–129 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Kikuyama, S. et al. Sodefrin: a female-attracting peptide pheromone in newt cloacal glands. Science 267, 1643–1645 (1995).

    Article  CAS  PubMed  Google Scholar 

  43. Kimoto, H., Haga, S., Sato, K. & Touhara, K. Sex-specific peptides from exocrine glands stimulate mouse vomeronasal sensory neurons. Nature 437, 898–901 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Potts, W. K. & Wakeland, E. K. Evolution of diversity at the major histocompatibility complex. Trends Ecol. Evol. 5, 181–186 (1990).

    Article  CAS  PubMed  Google Scholar 

  45. Klein, J. Natural History of the Major Histocompatibility Complex (John Wiley & Sons, New York, 1986).

    Google Scholar 

  46. Niedermann, G. et al. Potential immunocompetence of proteolytic fragments produced by proteasomes before evolution of the vertebrate immune system. J. Exp. Med. 186, 209–220 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Reits, E. A., Griekspoor, A. C. & Neefjes, J. How does TAP pump peptides? insights from DNA repair and traffic ATPases. Immunol. Today 21, 598–600 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Morgan, T. H. Removal of the block to self-fertilization in the ascidian Ciona. Proc. Natl Acad. Sci. USA 9, 170–171 (1923).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Marino, R., De Santis, R., Giuliano, P. & Pinto, M. R. Follicle cell proteasome activity and acid extract from the egg vitelline coat prompt the onset of self-sterility in Ciona intestinalis oocytes. Proc. Natl Acad. Sci. USA 96, 9633–9636 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sawada, H. et al. Self/nonself recognition in ascidian fertilization: vitelline coat protein HrVC70 is a candidate allorecognition molecule. Proc. Natl Acad. Sci. USA 101, 15615–15620 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cannon, J. P., Haire, R. N., Schnitker, N., Mueller, M. G. & Litman, G. W. Individual protochordates have unique immune-type receptor repertoires. Curr. Biol. 14, R465–R466 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Zhang, S. M., Adema, C. M., Kepler, T. B. & Loker, E. S. Diversification of Ig superfamily genes in an invertebrate. Science 305, 251–254 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Maizels, N. Immunoglobulin gene diversification. Annu. Rev. Genet. 39, 23–46 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Kyewski, B. & Derbinski, J. Self-representation in the thymus: an extended view. Nature Rev. Immunol. 4, 688–698 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I thank C. Bleul, N. Netuschil and M. Schorpp for discussions on the evolution of the adaptive immune system, and H. Breer, F. Zufall, P. Brennan and M. Milinski for their contributions to the experimental verification of some of the ideas discussed here.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Thomas Boehm's Laboratory

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Boehm, T. Co-evolution of a primordial peptide-presentation system and cellular immunity. Nat Rev Immunol 6, 79–84 (2006). https://doi.org/10.1038/nri1749

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri1749

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing