From specificity to degeneracy to molecular mimicry: antigen recognition of human autoreactive and pathogen-specific CD4+ T cells

  • B. Hemmer
  • C. Pinilla
  • B. Gran
  • H. F. McFarland
  • R. Houghten
  • R. Martin
Conference paper


Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). Although the cause of MS has not been identified, it is widely believed that myelin-specific T cells are somehow involved in the disease process [1]. However it is not clear how these cells become activated and mediate CNS disease. One of the most attractive models for the activation of autoreactive T cells is termed the “molecular mimicry hypothesis” [2]. According to this model, autoreactive T cells become activated in the peripheral immune system by crossreactive ligands derived from infectious agents. After activation and upregulation of adhesion molecules, these cells can cross the blood-brain barrier; after reactivation by myelin antigens either directly or via the recruitment of other cells, the activated T cells damage the myelin sheath and oligodendrocytes.


Myelin Basic Protein Molecular Mimicry Peptide Library Antigen Recognition Optimal Amino Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Martin R, McFarland HF, McFarlin DE (1992) Immunological aspects of demyelinating diseases. Annu Rev Immunol 10: 153–187PubMedCrossRefGoogle Scholar
  2. 2.
    Fujinami RS, Oldstone MBA (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230: 1043–1045PubMedCrossRefGoogle Scholar
  3. 3.
    Evavold BD, Sloan-Lancaster J, Wilson KJ, Rothbard JB, Allen PM (1995) Specific T cell recognition of minimally homologous peptides: evidence for endogenous ligands. Immunity 2: 655–663PubMedCrossRefGoogle Scholar
  4. 4.
    Wucherpfennig KW, Strominger JL (1995) Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80: 695–705PubMedCrossRefGoogle Scholar
  5. 5.
    Houghten RA (1985) General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci USA 82: 5131–5135PubMedCrossRefGoogle Scholar
  6. 6.
    Pinilla C, Appel JR, Houghten RA (1994) Investigation of antigen-antibody interactions using a soluble nonsupport-bound synthetic decapeptide library composed of four trillion sequences. Biochem J 301: 847–853PubMedGoogle Scholar
  7. 7.
    Vergelli M, Hemmer B, Kalbus M, Vogt AB, Ling N, Conlon P, Coligan JE, McFarland H, Martin R (1997) Modifications of peptide ligands enhancing T cell responsiveness imply large numbers of stimulatory ligands for autoreactive T cells. J Immunol 158: 3746–3752PubMedGoogle Scholar
  8. 8.
    Hemmer B, Fleckenstein BT, Vergelli M, Jung G, McFarland H, Martin R, Wiesmuller KH (1997) Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone. J Exp Med 185: 1651–1659PubMedCrossRefGoogle Scholar
  9. 9.
    Hemmer B, Pinilla C, Appel J, Pascal J, Houghten R, Martin R (1998) The use of soluble synthetic peptide combinatorial libr dries to determine antigen recognition of T cells. J Pept Res 52: 338–345PubMedCrossRefGoogle Scholar
  10. 10.
    Hemmer B, Vergelli M, Pinilla C, Houghten R, Martin R (1998) Probing degeneracy in T cell recognition using peptide combinatorial libraries. Immunol Today 19: 163–168PubMedCrossRefGoogle Scholar
  11. 11.
    Kisielow P, von Boehmer H (1995) Development and selection of T cells: facts and puzzles. Adv Immunol 58: 87–209PubMedCrossRefGoogle Scholar
  12. 12.
    Kirberg J, Berns A, von Boehmer H (1997) Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules. J Exp Med 186: 1269–1275PubMedCrossRefGoogle Scholar
  13. 13.
    Hemmer B, Vergelli M, Gran B, Ling N, Conlon P, Pinilla C, Houghten R, McFarland HF, Martin R (1998) Cutting edge: Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology. J Immunol 160: 3631–3636PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milan 1999

Authors and Affiliations

  • B. Hemmer
  • C. Pinilla
  • B. Gran
  • H. F. McFarland
  • R. Houghten
  • R. Martin

There are no affiliations available

Personalised recommendations