Abstract

Three areas of study are covered in the final year of this grant. We are continuing investigations of the mechanism of reaction of anti-I-A antibody in reversing experimental allergic encephalomyelitis (EAE). T cell clones which induce EAE are central to this aspect of this study. These T cell clones are restricted to I-A molecules and recognize specific peptides on myelin basic protein. The second part of this investigation involves monoclonal antibodies directed against T cell subset markers. An antibody to the L3T4 antigen on helper/inducer T cells has been shown to reverse EAE as effectively as anti I-A antibody. The mechanism underlying this observation will be studied. Finally, we are using transposon induced mutations in Bordetella pertussis to design a safer pertussis vaccine. We have shown that transposon induced mutations which markedly reduce the amount of pertussis toxin available in these organisms leads to a greatly reduced encephalopathic potential.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000571-05
Application #
3078055
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1981-03-01
Project End
1986-06-30
Budget Start
1985-03-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Steinman, L (1988) Therapy of autoimmune disease with monoclonal antibodies to class II gene products of the major histocompatibility complex. Prog Allergy 45:161-7
Bell, J I; Steinman, L; Toyka, K et al. (1987) HLA-DQ restriction fragment length polymorphisms in myasthenia gravis. Ann N Y Acad Sci 505:382-7
Waldor, M K; O'Hearn, M; Sriram, S et al. (1987) Treatment of experimental autoimmune myasthenia gravis with monoclonal antibodies to immune response gene products. Ann N Y Acad Sci 505:655-68
Bell, J; Rassenti, L; Smoot, S et al. (1986) HLA-DQ beta-chain polymorphism linked to myasthenia gravis. Lancet 1:1058-60
Zamvil, S S; Mitchell, D J; Moore, A C et al. (1986) T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324:258-60
Zamvil, S; Nelson, P; Trotter, J et al. (1985) T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317:355-8
Steinman, L; Trotter, J; Waldor, M et al. (1985) New approaches to therapy of autoimmune disease. Concepts Immunopathol 1:85-95
Steinman, L; Weiss, A; Adelman, N et al. (1985) Pertussis toxin is required for pertussis vaccine encephalopathy. Proc Natl Acad Sci U S A 82:8733-6
Steinman, L; Weiss, A; Adelman, N et al. (1985) Murine model for pertussis vaccine encephalopathy: role of the major histocompatibility complex;antibody to albumin and to Bordetella pertussis and pertussis toxin. Dev Biol Stand 61:439-46
Trotter, J; Sriram, S; Rassenti, L et al. (1985) Characterization of T cell lines and clones from SJL/J and (BALB/c x SJL/J)F1 mice specific for myelin basic protein. J Immunol 134:2322-7

Showing the most recent 10 out of 11 publications