Myelin basic protein, MHC restriction molecules and T cell repertoire.

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Abstract

Our laboratory has developed a broad base of information in rats and mice describing the properties of encephalitogenic T cells. Using the T cell line selection technique to identify dominant T cell specificities, we were the first to identify new encephalitogenic epitopes and MHC restriction molecules in the Lewis rat and the SJL mouse. Furthermore, using the soft agar technique, we have isolated encephalitogenic Lewis rat T cell clones specific for defined synthetic epitopes of BP. With our colleagues, we have identified and sequenced the V region genes, and deduced the amino acid sequence of proteins which these clones use preferentially in their T cell receptor. Furthermore, we have successfully induced protection against EAE by the lymphocyte vaccination approach, using attenuated encephalitogenic T cells as the vaccine. Using this information, we have made significant progress in characterizing and understanding human T lymphocyte responses to BP. Recent results indicate that MBP reactivity is more frequent in MS patients than in controls, suggesting a greater degree of sensitization, and a potential involvement of BP as a target antigen. Since human BP responses also appear to be directed at immunodominant epitopes (as we have observed in rodents), it is probable that human T cells will also use preferential combinations of T cell receptor V genes. The ability to induce specific regulation or removal of autoreactive T cells will allow for the first time an assessment of cause and effect in human diseases. Immunoregulation directed at the TCR polypeptides may allow selective suppression of encephalitogenic clones, and may have direct application in human diseases such as MS, or in other autoimmune situations where preferential TCR V gene usage can be identified.

Original languageEnglish (US)
Pages (from-to)93-108
Number of pages16
JournalProgress in Clinical and Biological Research
Volume336
StatePublished - 1990

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Myelin Basic Protein
T-Lymphocytes
Clone Cells
Epitopes
T-Cell Antigen Receptor Specificity
T-Cell Receptor Genes
Immunodominant Epitopes
T-Cell Antigen Receptor
Genes
Agar
Amino Acid Sequence
Rodentia
Vaccination
Vaccines
Lymphocytes
Antigens
Cell Line
Peptides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Myelin basic protein, MHC restriction molecules and T cell repertoire. / Vandenbark, Arthur; Hashim, G.; Offner, Halina.

In: Progress in Clinical and Biological Research, Vol. 336, 1990, p. 93-108.

Research output: Contribution to journalArticle

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