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
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 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
Medzhitov, R. & Janeway, C. A. Jr. Decoding the patterns of self and nonself by the innate immune system. Science 296, 298–300 (2002).
Lanier, L. L. NK cell recognition. Annu. Rev. Immunol. 23, 225–274 (2005).
Pancer, Z. et al. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature 430, 174–180 (2004).
Pancer, Z. et al. Variable lymphocyte receptors in hagfish. Proc. Natl Acad. Sci. USA 102, 9224–9229 (2005).
Tonegawa, S. Somatic generation of antibody diversity. Nature 302, 575–581 (1983).
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).
Sakano, H., Huppi, K., Heinrich, G. & Tonegawa, S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature 280, 288–294 (1979).
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).
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).
Kapitonov, V. V. & Jurka, J. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biol. 3, e181 (2005).
Landsteiner, K. & van der Scheer, J. Serological differentiation of steric isomers. J. Exp. Med. 48, 315–320 (1928).
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).
Eason, D. D. et al. Mechanisms of antigen receptor evolution. Semin. Immunol. 16, 215–226 (2004).
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).
Trombetta, E. S. & Mellman, I. Cell biology of antigen processing in vitro and in vivo. Annu. Rev. Immunol. 23, 975–1028 (2005).
Huseby, E. S. et al. How the T cell repertoire becomes peptide and MHC specific. Cell 122, 247–260 (2005).
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).
Rudolph, M. G. & Wilson, I. A. The specificity of TCR/pMHC interaction. Curr. Opin. Immunol. 14, 52–65 (2002).
Hogquist, K. A., Baldwin, T. A. & Jameson, S. C. Central tolerance: learning self-control in the thymus. Nature Rev. Immunol. 5, 772–782 (2005).
Rammensee, H. G., Bachmann, J. & Stefanovic, S. MHC Ligands and Peptide Motifs (Landes Bioscience, Georgetown, Texas, 1997).
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).
Lopez de Castro, J. A. et al. HLA-B27: a registry of constitutive peptide ligands. Tissue Antigens 63, 424–445 (2004).
Bjorkman, P. J. & Parham, P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu. Rev. Biochem. 59, 253–288 (1990).
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).
Penn, D. & Potts, W. How do major histocompatibility complex genes influence odour and mating preferences? Adv. Immunol. 69, 411–436 (1998).
Ziegler, A., Kentenich, H. & Uchanska-Ziegler, B. Female choice and the MHC. Trends Immunol. 26, 496–502 (2005).
Singh, P. B., Brown, R. E. & Roser, B. MHC antigens in urine as olfactory recognition cues. Nature 327, 161–164 (1987).
Leinders-Zufall, T. et al. MHC class I peptides as chemosensory signals in the vomeronasal organ. Science 306, 1033–1037 (2004).
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).
Bruce, H. M. An exteroceptive block to pregnancy in the mouse. Nature 184, 105 (1959).
Yamazaki, K. et al. Recognition of H-2 types in relation to the blocking of pregnancy in mice. Science 221, 186–188 (1983).
Brennan, P., Kaba, H. & Keverne, E. B. Olfactory recognition: a simple memory system. Science 250, 1223–1226 (1990).
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).
Brennan, P. A. & Keverne, E. B. Something in the air? New insights into mammalian pheromones. Curr. Biol. 14, R81–R89 (2004).
Mombaerts, P. Genes and ligands for odorant, vomeronasal and taste receptors. Nature Rev. Neurosci. 5, 263–278 (2004).
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).
Brown, A. J. & Casselton, L. A. Mating in mushrooms: increasing the chances but prolonging the affair. Trends Genet. 17, 393–400 (2001).
Kronstad, J. W. & Staben, C. Mating type in filamentous fungi. Annu. Rev. Genet. 31, 245–276 (1997).
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).
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).
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).
Kikuyama, S. et al. Sodefrin: a female-attracting peptide pheromone in newt cloacal glands. Science 267, 1643–1645 (1995).
Kimoto, H., Haga, S., Sato, K. & Touhara, K. Sex-specific peptides from exocrine glands stimulate mouse vomeronasal sensory neurons. Nature 437, 898–901 (2005).
Potts, W. K. & Wakeland, E. K. Evolution of diversity at the major histocompatibility complex. Trends Ecol. Evol. 5, 181–186 (1990).
Klein, J. Natural History of the Major Histocompatibility Complex (John Wiley & Sons, New York, 1986).
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).
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).
Morgan, T. H. Removal of the block to self-fertilization in the ascidian Ciona. Proc. Natl Acad. Sci. USA 9, 170–171 (1923).
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).
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).
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).
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).
Maizels, N. Immunoglobulin gene diversification. Annu. Rev. Genet. 39, 23–46 (2005).
Kyewski, B. & Derbinski, J. Self-representation in the thymus: an extended view. Nature Rev. Immunol. 4, 688–698 (2004).
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
Ethics declarations
Competing interests
The author declares no competing financial interests.
Related links
Rights 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
Issue Date:
DOI: https://doi.org/10.1038/nri1749
This article is cited by
-
Origin and evolutionary malleability of T cell receptor α diversity
Nature (2023)
-
Of volatiles and peptides: in search for MHC-dependent olfactory signals in social communication
Cellular and Molecular Life Sciences (2014)
-
A whiff of genome
Nature (2013)
-
Design principles of adaptive immune systems
Nature Reviews Immunology (2011)
-
The origins of vertebrate adaptive immunity
Nature Reviews Immunology (2010)