T LYMPHOCYTE LINES SPECIFIC FOR MYELIN BASIC PROTEIN

Project: Research project

Project Details

Description

This proposal is based upon recent data obtained during a visit to the
Weizmann Institute, Rehovot, Israel. These data suggested that T
lymphocyte lines from different rat strains recognized different regions of
the myelin basic protein molecule, and that the recognition pattern was
dictated by the antigen presenting cell. The dominant region of BP for
each strain was able to stimulate T cell reactivity which induced paralytic
disease (EAE) as well as protection from subsequent induction of disease. Because BP may be relevant neuroantigen in human paralytic diseases such as
multiple sclerosis (MS), and because responsiveness to regions of BP could
be regulated by the major histocompatibility complex (MHC), we propose to
evaluate the immunodominant regions of BP in normal volunteers and MS
patients in the context of Class II MHC antigens. This evalution will be
accomplished by selecting BP specific T cell lines, cloning these lines,
and then evaluting responsiveness to purified fragments of BP. The role of
Class II MHC antigens will be inferred from HLA-D typing results, by
stimulation of T cell clones with antigen presenting cells with partial
identity in the HLA-D region, and by inhibition of HLA-DR, DP, and DQ
dependent activation of T cell clones. From these data, we hope to determine 1) what regions of human BP stimulate
human T cells, 2) the number of immunodominant determinants recognized by
each individual, 3) whether the range and distribution of T cell responses
differ in normal individuals and MS patients, and 4) whether HLA-D region
gene products are associated with T cell recognition of human BP
determinants.
StatusFinished
Effective start/end date8/1/863/31/11

Funding

  • National Institutes of Health: $377,500.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $368,351.00
  • National Institutes of Health: $377,500.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $361,234.00
  • National Institutes of Health
  • National Institutes of Health: $377,500.00
  • National Institutes of Health: $377,500.00
  • National Institutes of Health: $350,713.00
  • National Institutes of Health
  • National Institutes of Health: $350,659.00
  • National Institutes of Health
  • National Institutes of Health: $377,500.00
  • National Institutes of Health
  • National Institutes of Health: $350,707.00
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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