Skip to main content

Advertisement

SpringerLink
Log in

CD91 up-regulates upon immune stimulation in Xenopus adult but not larval peritoneal leukocytes

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

CD91, the endocytic receptor for α2-macroglobulin (α2M), mediates the internalization of certain heat shock proteins (hsps) and the cross-presentation of peptides they chaperone by antigen-presenting cells. The phylogenetic conservation of the immunologically active CD91 ligands, α2M and hsps, is consistent with the idea of an ancestral system of immune surveillance. We have further explored this hypothesis by taking advantage of the frog Xenopus, and asked how conserved is CD91 and whether the expression of CD91 is differentially modulated during immune responses of class I-positive adult and naturally class I-negative larvae. We have identified a Xenopus CD91 gene homologue that displays high sequence identity (>65%) with other CD91 homologues and contains an additional distinctive cytoplasmic NPXY motif. Phylogenetic analysis indicates that CD91 homologues branch as a monophyletic group distinct from other LDLRs; this suggests an origin of CD91 contemporary with that of metazoans. A 14-kb transcript is detected by Northern blotting in most adult and larval tissues, including lymphoid tissues. RT-PCR study reveals that CD91 is expressed in most cell types, including adult macrophages, B and T cells as well as in splenocytes and thymocytes from naturally MHC class I negative larvae. CD91 is markedly up-regulated in vivo by adult peritoneal leukocytes following bacterial and viral stimulation; it is constitutively expressed on class I-negative larval peritoneal leukocytes at high levels and cannot be further upregulated by such stimulation. These data are in agreement with a conserved role of CD91 in immunity.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4a–c
Fig. 5
Fig. 6a,b
Fig. 7

Similar content being viewed by others

References

  • Armstrong PB, Quigley JP (1999) α2-macroglobulin: an evolutionarily conserved arm of the innate immune system. Dev Comp Immunol 23:375–390

    Article  CAS  PubMed  Google Scholar 

  • Basu S, Binder R, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock protein gp96, hsp90, hsp70, and calreticulin. Immunity 14:303

    Article  CAS  PubMed  Google Scholar 

  • Banerjee PP, Vinay DS, Mathew A, Raje M, Parekh V, Prasad DV, Kumar A, Mitra D, Mishra GC (2002) Evidence that glycoprotein 96 (B2), a stress protein, functions as a Th2-specific costimulatory molecule. J Immunol 169:3507–3518

    CAS  PubMed  Google Scholar 

  • Bevan MJ (1995) Antigen presentation to cytotoxic T lymphocytes in vivo. J Exp Med 182:639–641

    Article  CAS  PubMed  Google Scholar 

  • Binder R, Srivastava PK (2004) Essential role of CD91 in re-presentation of gp96-chaperoned peptides. Proc Natl Acad Sci USA 101:6128–6133

    Article  CAS  PubMed  Google Scholar 

  • Binder R, Han D, Srivastava PK (2000) CD91: a receptor for heat shock protein gp96. Nat Immunol 1:151–155

    Article  CAS  PubMed  Google Scholar 

  • Borth W (1994) Alpha 2-macroglobulin. A multifunctional binding and targeting protein with possible roles in immunity and autoimmunity. Ann N Y Acad Sci 737:267–272

    CAS  PubMed  Google Scholar 

  • Castellino F, Boucher P, Eichelberg K, Mayhew M, Rothman J, Houghton A, Germain R (2000) Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways. J Exp Med 191:1957–1964

    Article  CAS  PubMed  Google Scholar 

  • Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J, Jeannin P (2002) Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 17:353–362

    Article  CAS  PubMed  Google Scholar 

  • Du Pasquier L, Flajnik MF (1990) Expression of MHC class II antigens during Xenopus development. Dev Immunol 1:85–95

    PubMed  Google Scholar 

  • Du Pasquier L, Schwager J, Flajnik MF (1989) The immune system of Xenopus. Annu Rev Immunol 7:251–275

    Article  PubMed  Google Scholar 

  • Flajnik MF, Taylor E, Canel C, Grossberger D, Du Pasquier L (1991) Reagents specific for MHC I antigens of Xenopus. Am Zool 31:580–591

    CAS  Google Scholar 

  • Gantress J, Bell A, Maniero G, Cohen N, Robert J (2003) Xenopus, a model to study immune response to iridovirus. Virology 311:254–262

    Article  CAS  PubMed  Google Scholar 

  • Habich C, Baumgart K, Kolb H, Burkart V (2002) The receptor for heat shock protein 60 on macrophages is saturable, specific, and distinct from receptors for other heat shock proteins. J Immunol 168:569–576

    CAS  PubMed  Google Scholar 

  • Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley K (1988) Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. EMBO J 7:4119–4127

    CAS  PubMed  Google Scholar 

  • Herz J, Kowal R, Goldstein J, Brown M (1990) Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment. EMBO J 9:1776–1990

    Google Scholar 

  • Herz J, Strickland DK (2001) LRP: A multifunctional scavenger and signaling receptor. J Clin Invest 108:779–784

    Article  CAS  PubMed  Google Scholar 

  • Jancovich JK, Davidson EW, Morado JF, Jacobs BL, Collins JP (1997) Isolation of a lethal virus from the endangered tiger salamander Ambystoma tigrinum stebbins. Dis Aquat Org 31:161–167

    Google Scholar 

  • Krieg P, Varnum S, Wormington W, Melton D (1989) The mRNA encoding elongation factor 1-alpha (EF-alpha) is a major transcript at the midblastula transition in Xenopus. Dev Biol 133:93–100

    Article  CAS  PubMed  Google Scholar 

  • Kristensen T, Moestrup SK, Gliemann J, Bendtsen L, Sand O, Sottrup-Jensen L (1990) Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor. FEBS Lett 276:151–155

    Article  CAS  PubMed  Google Scholar 

  • Nassar T, Akkawi S, Bar-Shavit R, Haj-Yehia A, Bdeir K, Al-Mehdi AB, Tarshis M, Higazi AA (2002) Human alpha-defensin regulates smooth muscle cell contraction: A role for low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. Blood 100:4026–4032

    Article  CAS  PubMed  Google Scholar 

  • Nieuwkoop PD, Faber J (1967) Normal tables of Xenopus laevis (Daudin), North-Holland, Amsterdam

  • Robert J (2003) Evolution of heat shock proteins and immunity. Dev Comp Immunol 27:449–464

    Article  CAS  PubMed  Google Scholar 

  • Robert J, Du Pasquier L (1997) Xenopus lymphoid tumor cell lines. In: Lefkovitz I (ed) Manual of immunological methods. Academic Press, London, pp 2367-2377

    Google Scholar 

  • Robert J, Guiet C, Du Pasquier L (1994) Lymphoid tumors of Xenopus laevis with different capacities for growth in larvae and adults. Devel Immunol 3:297–307

    CAS  Google Scholar 

  • Robert J, Gantress J, Rau L, Bell A, Cohen N (2002) Minor histocompatibility antigen-specific MHC-restricted CD8 T-cell responses elicited by heat shock proteins. J Immunol 168:1697–1703

    CAS  PubMed  Google Scholar 

  • Salter-Cid L, Nonaka M, Flajnik MF (1998) Expression of MHC class Ia and class Ib during ontogeny: High expression in epithelia and coregulation of class Ia and lmp7 genes. J Immunol 160:2853–2861

    CAS  PubMed  Google Scholar 

  • Singh-Jasuja H, Scherer HU, Hilf N, Arnold-Schild D, Rammensee HG, Toes RE, Schild H (2000) The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. Eur J Immunol 30:2211–2215

    CAS  PubMed  Google Scholar 

  • Stebbing J, Gazzard B, Kim L, Portsmouth S, Wildfire A, Teo I, Nelson M, Bower M, Gotch F, Shaunak S, Srivastava P, Patterson S (2003) The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected “true” long-term nonprogressors. Blood 101:4000–4004

    Article  CAS  PubMed  Google Scholar 

  • Srivastava P (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: Chaperoning of the innate and adaptive immune responses. Annu Rev Immunol. 20:395–425

    Article  CAS  PubMed  Google Scholar 

  • Strickland DK, Ashcom JD, Williams S, Burgess WH, Migliorini M, Argraves WS (1990) Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor. J Biol Chem 265:17401–17404

    CAS  PubMed  Google Scholar 

  • Suto R, Srivastava PK (1995) A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269:1585–1588

    CAS  PubMed  Google Scholar 

  • Tobian AA, Canaday DH, Boom WH, Harding CV (2004) Bacterial heat shock proteins promote CD91-dependent class I MHC cross-presentation of chaperoned peptide to CD8+ T cells by cytosolic mechanisms in dendritic cells versus vacuolar mechanisms in macrophages. J Immunol 172:5277–5286

    CAS  PubMed  Google Scholar 

  • Williams SE, Kounnas MZ, Argraves KM, Argraves WS, Strickland DK (1994) The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and the receptor-associated protein. An overview. Ann N Y Acad Sci 737:1–13

    Google Scholar 

  • Yochem J, Greenwald I (1993) A gene for a low density lipoprotein receptor-related protein in the nematode Caenorhabditis elegans. Proc Natl Acad Sci USA 90:4572–4576

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Larry Dishaw for advice concerning phylogenetic analysis, Dr. Nicholas Cohen for advice and critical review of the manuscript and David Albright for his expert animal husbandry. This research was supported by grants R25-GM64133 (S.M.), T32 A107285 (G.M.), RO1 AI-44011 from the NIH, and MCB-0136536 and IRCEB-001388 from the NSF.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology,, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Shauna Marr, Ana Goyos, Jennifer Gantress & Jacques Robert

  2. Department of Biology, Stonehill College, Easton, MA, 02356, USA

    Gregory D. Maniero

Authors
  1. Shauna Marr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Goyos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jennifer Gantress
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory D. Maniero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jacques Robert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacques Robert.

Additional information

S. Marr and A. Goyos contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marr, S., Goyos, A., Gantress, J. et al. CD91 up-regulates upon immune stimulation in Xenopus adult but not larval peritoneal leukocytes. Immunogenetics 56, 735–742 (2005). https://doi.org/10.1007/s00251-004-0736-4

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-004-0736-4

Keywords

Search

Navigation