Immunologic Research

, Volume 26, Issue 1–3, pp 77–85 | Cite as

Inhibition of T cell responses by transferrin-coupled competitor peptides

  • Lolita Zaliauskiene
  • Rebecca L. Fazio
  • Sunghyun Kang
  • Kerri Sparks
  • Casey T. Weaver
  • Kurt R. Zinn
  • James F. Collawn
Article

Abstract

Activation of helper T cell has been implicated in a number of autoimmune diseases including rheumatoid arthritis. The underlying mechanism that initiates and promotes disease progression remains unclear, but it is apparent that helper T cells and autoantigens play prominentroles. Identification of the autoantigens has proven to be extremely difficult, and therefore strategies for promoting tolerance induction remain limited. Since autoimmune diseases are closely associated with specific major histocompatibility complex class II molecules such as HLA-DR4, the use of competitor peptides is an alternative strategy. A limitation of competitor peptides, however, is that they are ineffective in vivo. In the studies presented here, we demonstrate that coupling competitor peptides to a cell-surface receptor ligand, transferrin, enhances their ability to block helper T cell responses using the DO11.10 transgenic mouse as our model system.

Key Words

Competitor peptides Transferrin Major histocompatibility complex class II Autoreactive T cells Immunosuppression 

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References

  1. 1.
    Svejgaard A, Platz P, Ryder LP: HLA and disease 1982—a survey. Immunol Rev 1983;70:193–218.PubMedCrossRefGoogle Scholar
  2. 2.
    Werdelin O: Chemically related antigens complete for presentation by accessory cells to T cells. J Immunol 1982;129:1883–1891.PubMedGoogle Scholar
  3. 3.
    Babbitt BP, Matsueda G, Haber E, Unanue ER, Allen PM: Antigenic competition at the level of peptidela binding. Proc Natl Acad Sci USA 1986;83:4509–4513.PubMedCrossRefGoogle Scholar
  4. 4.
    Adorini L, Muller S, Cardinaux F, Lehmann PV, Falcioni F, Nagy ZA: In vivo competition between self peptides and foreign antigens in T-cell activation. Nature 1988;334:623–625.PubMedCrossRefGoogle Scholar
  5. 5.
    Lorenz RG, Blum JS, Allen PM: Constitutive competition by self proteins for antigen presentation can be overcome by receptor-enhanced uptake. J Immunol 1990; 144:1600–1606.PubMedGoogle Scholar
  6. 6.
    Lanzavecchia A: Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. Annu Rev Immunol 1990;8: 773–793.PubMedGoogle Scholar
  7. 7.
    Legge KL, Min B, Potter NT, Zaghouani H: Presentation of a T cell receptor antagonist peptide by immunoglobulins ablates activation of T cells by asynthetic peptide or proteins requiring endocytic processing. J. Exp Med 1997;185: 1043–1053.PubMedCrossRefGoogle Scholar
  8. 8.
    Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC: Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 2001;194:769–779.PubMedCrossRefGoogle Scholar
  9. 9.
    Lock C, Smilek D, Gautam A, Vaysburd M, Dwivedy S, McDevitt H: Competitive inhibition of antigen presentation in animal models of autoimmune disease. Semin Immunol 1991;3:247–255.PubMedGoogle Scholar
  10. 10.
    Ravetch JV, Bolland S: IgG Fc receptors. Annu Rev Immunol 2001; 19:275–290.PubMedCrossRefGoogle Scholar
  11. 11.
    Tschoetschel U, McCoy KL, Reske-Kunz AB: Augmented antigen presentation by mouse Ia+ T clone cells BK-BI-2.6.04. Imediated by transferrin receptors. Scand. J. Immunol 1996;43:500–506.PubMedCrossRefGoogle Scholar
  12. 12.
    McCoy KL, Noone M, Imman JK, Stutzman R: Exogenous antigens internalized through transferrin receptors activate CD4+ T cells. J Immunol 1993;150:1691–1704.PubMedGoogle Scholar
  13. 13.
    Niebling WL, Pierce SK: Antigen entry into early endosomes is insufficient for mhc class II processing. J Immunol 1993;150:2687–2697.PubMedGoogle Scholar
  14. 14.
    Mauri D, Wyss-Coray T, Brander C, Pichler WJ: Improved sensitization of antigen-presenting cells with transferrin-bound peptides: advantages in competition for antigen presentation. Cell Immunol 1994;158:59–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Mellman I, Turley SJ, Steinman RM: Antigen processing for amateurs and professionals. Trends Cell Biol 1998;8:231–237.PubMedCrossRefGoogle Scholar
  16. 16.
    Zaliauskiene L, Kang S, Brouillette C, Lebowitz J, Arani RB, Collawn JF: Down-regulation of cell surface receptors is modulated by polar residues within the transmembrane domains. Mol Biol Cell 2000;11(8): 2643–2655.PubMedGoogle Scholar
  17. 17.
    Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998;392:245–252.PubMedCrossRefGoogle Scholar
  18. 18.
    Ceppellini R, Frumento G, Ferrara GB, Rosi R, Chersi A, Perrnis B: Binding of labelled influenza matrix peptide to HLA DR in living B lymphoid cells. Nature 1989; 339:392–394.PubMedCrossRefGoogle Scholar
  19. 19.
    Zinn KR, Douglas JT, Smyth CA, Liu H-G, Wu Q, Krasnykh VN, Mountz JD, Curriel DT, Mountz JM: Imaging and tissue biodistribution of 99m Tc-labeled adenovirus knob (serotype 5). Gene Ther 1998;5:798–808.PubMedCrossRefGoogle Scholar
  20. 20.
    Kearney ER, Pape KA, Loh DY, Jenkins MK: Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity 1994;1:327–339.PubMedCrossRefGoogle Scholar
  21. 21.
    Liu H, Rhodes M, Wiest DL, Vignali DA: On the dynamics of TCR:CD3 complex cell surface expression and downmodulation. Immunity 2000;13:665–675.PubMedCrossRefGoogle Scholar
  22. 22.
    Fulcher DA, Lyons AB, Kom SL, Cook MC, Koleda C, Parish C, Fazekas de St Groth B, Basten A: The fate of self-reactive B cells depends primarity on the degree of antigen receptor engagement and availability of T cell help. J. Exp. Med 1996;183:2313–2328.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Lolita Zaliauskiene
    • 1
    • 2
  • Rebecca L. Fazio
    • 1
    • 2
  • Sunghyun Kang
    • 1
    • 2
  • Kerri Sparks
    • 1
    • 2
  • Casey T. Weaver
    • 3
  • Kurt R. Zinn
    • 4
  • James F. Collawn
    • 1
    • 2
  1. 1.Department of Cell BiologyUniversity of Alabama at BirminghamBirmingham
  2. 2.UAB Comprehensive Cancer CenterUniversity of Alabama at BirminghamBirmingham
  3. 3.Department of PathologyUniversity of Alabama at BirminghamBirmingham
  4. 4.Department of RadiologyUniversity of Alabama at BirminghamBirmingham

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