Cell
Volume 54, Issue 4, 12 August 1988, Pages 577-592
Journal home page for Cell

Article
Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy

https://doi.org/10.1016/0092-8674(88)90079-7Get rights and content

Abstract

Experimental allergic encephalomyelitis (EAE) is a paralytic autoimmune disease induced in susceptible animals by active immunization with myelin basic protein (MBP) or by passive transfer of MBP-specific T helper (TH) lymphocytes. We have analyzed the T cell receptor genes of 33 clonally distinct TH cells specific for a nonapeptide of MBP inducing EAE in B10.PL (H-2u) mice. All 33 TH cells used two α variable gene segments (Vα2.3, 61%; Vα4.2, 39%), the same α joining gene segment (Jα39), and two Vβ and Jβ gene segments (Vβ8.2-Jβ2.6, 79%; Vβ 13-Jβ 2.2, 21%). The anti-Vβ8 monoclonal antibody F23.1 was found to block completely recognition of the nonapeptide by Vβ8 TH cells in vitro and to reduce significantly the susceptibility of B10.PL mice to peptide-induced EAE.

References (78)

  • E.C. Alvord et al.

    Encephalitogen-induced inhibition of experimental allergic encephalomyelitis: prevention, suppression, and therapy

    Ann. NY Acad. Sci.

    (1965)
  • L.M. Amzel et al.

    The three dimensional structure of a combining region-ligand complex of immunoglobulin NEW at 3.5Å resolution

  • B. Arden et al.

    Diversity and structure of genes of the α family of mouse T-cell antigen receptor

    Nature

    (1985)
  • R.K. Barth et al.

    The murine T-cell receptor uses a limited repertoire of expressed Vβ gene segments

    Nature

    (1985)
  • M.A. Behlke et al.

    Alternative splicing of murine T-cell receptor β-chain transcripts

    Nature

    (1986)
  • M.A. Behlke et al.

    T-cell receptor β-chain expression: dependence on relatively few variable region genes

    Science

    (1985)
  • A. Ben-Nun et al.

    Vaccination against autoimmune encephalomyelitis with T-lymphocyte line cells reactive against myelin basic protein

    Nature

    (1981)
  • S.W. Brostoff et al.

    Experimental allergic encephalomyelitis: successful treatment in vivo with a monoclonal antibody that recognizes T helper cells

    J. Immunol.

    (1984)
  • Y. Chien et al.

    A third type of murine T cell receptor gene

    Nature

    (1984)
  • Y.-H. Chien et al.

    Somatic recombination in a murine T cell receptor gene

    Nature

    (1984)
  • J.M. Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
  • H.S. Chou et al.

    Tandem linkage and unusual RNA splicing of the T-cell receptor β-chain variable-region genes

  • S.H. Clarke et al.

    Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin

    J. Exp. Med.

    (1985)
  • I. Clark-Lewis et al.

    Automated chemical synthesis of a protein growth factor for hemopoietic cells, interleukin-3

    Science

    (1986)
  • P.C. Doherty et al.

    H-2 compatibility is required for T-cell mediated types of target cells infected with lymphocytic choriomeningitis virus

    J. Exp. Med.

    (1975)
  • P.J. Fink et al.

    Correlations between T-cell specificity and the structure of the antigen receptor

    Nature

    (1986)
  • R.B. Fritz et al.

    Major histocompatibility complex-linked control of the murine response to myelin basic protein

    J. Immunol.

    (1985)
  • N.R. Gascoigne et al.

    Genomic organization and sequence of T-cell receptor β-chain constant and joining-region genes

    Nature

    (1984)
  • S. Gillis et al.

    T-cell growth factor: parameters of production and quantitative microassay for activity

    J. Immunol.

    (1978)
  • K. Haskins et al.

    The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype

    J. Exp. Med.

    (1984)
  • A.C. Hayday et al.

    Unusual organization and diversity of T-cell receptor α-chain genes

    Nature

    (1985)
  • S.M. Hedrick et al.

    Isolation of cDNA clones encoding T cell-specific membrane-associated proteins

    Nature

    (1984)
  • S.M. Hedrick et al.

    Selection of amino acid sequences in the beta chain of the T-cell antigen receptor

    Science

    (1988)
  • P.J. Higgins et al.

    Suppression of experimental allergic encephalomyelitis by oral administration of myelin basic protein and its fragments

    J. Immunol.

    (1988)
  • J.H. Hold et al.

    Autoimmune effector cells. I. Transfer of experimental allergic encephalomyelitis with lymphoid cells cultured with antigen

    Eur. J. Immunol.

    (1980)
  • A. Iwamoto et al.

    T cell receptor variable gene usage in a specific cytotoxic T cell response

    Primary structure of the antigen-MHC receptor of four hapten-specific cytotoxic T cell clones

    J. Exp. Med.

    (1987)
  • J. Kappler et al.

    Antigen-inducible, H-2-restricted, interleukin-2 producing T-cell hybridomas

    Lack of independent antigen and H-2 recognition

    J. Exp. Med.

    (1981)
  • D.H. Katz et al.

    Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interaction between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates

    J. Exp. Med.

    (1973)
  • M. Kimoto et al.

    Antigen-reactive T cell clones. I. Trans complementing hybrid I-A-region gene products function effectively in antigen presentations

    J. Exp. Med.

    (1980)
  • Cited by (603)

    • Rapamycin and MCC950 modified gut microbiota in experimental autoimmune encephalomyelitis mouse by brain gut axis

      2020, Life Sciences
      Citation Excerpt :

      Neurological function scores and body weight were measured on the second day after immunization. The international Kono's 5-point scoring system [12] was used for clinical scoring of mice. Starting from the 3th day after being immunized with MOG35–55, RAPA group injected intraperitoneal with rapamycin (1 mg/kg) every other day.

    • T-cell repertoire profiling by next-generation sequencing reveals tissue migration dynamics of TRBV13-family clonotypes in a common experimental autoimmune encephalomyelitis mouse model

      2019, Journal of Neuroimmunology
      Citation Excerpt :

      In the MBP model, there is a strong overlap of the encephalitogenic epitopes between mice and humans (Sospedra and Martin, 2005). Moreover, V-gene restriction of myelin reactive T-cells leading to an oligoclonal T-cell repertoire has been especially found in MBP-induced mouse models (Acha-Orbea et al., 1988; Urban et al., 1988), a phenomenon that is also observed in MS patients (Hafler et al., 1996; Planas et al., 2018). Based on these findings, specific TCR directed therapies targeting the restricted repertoire were developed, although with little success (Killestein et al., 2002; Vandenbark et al., 2008; Wraith, 2009).

    • Treatment with tanshinone IIA suppresses disruption of the blood-brain barrier and reduces expression of adhesion molecules and chemokines in experimental autoimmune encephalomyelitis

      2016, European Journal of Pharmacology
      Citation Excerpt :

      The day of immunization was designated Day 0. The animals were weighed twice a day, and neurological deficits were assessed every day according to a five point scoring system (Urban et al., 1988) by two independent blinded observers. The following scores were assigned: 0=no signs, 1=flaccid tail, 2=impairment of fighting reflex and/or loss of muscle tone in hind limbs, 3=complete paralysis of hind limbs, 4=paraplegia, and 5=moribund state/death.

    View all citing articles on Scopus
    View full text