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Myelin basic protein, MHC restriction molecules and T cell repertoire.
Prog Clin Biol Res. 1990; 336:93-108.PC

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.

Authors+Show Affiliations

Department of Neurology, Oregon Health Sciences University, Portland 97201.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

1691512

Citation

Vandenbark, A A., et al. "Myelin Basic Protein, MHC Restriction Molecules and T Cell Repertoire." Progress in Clinical and Biological Research, vol. 336, 1990, pp. 93-108.
Vandenbark AA, Hashim G, Offner H. Myelin basic protein, MHC restriction molecules and T cell repertoire. Prog Clin Biol Res. 1990;336:93-108.
Vandenbark, A. A., Hashim, G., & Offner, H. (1990). Myelin basic protein, MHC restriction molecules and T cell repertoire. Progress in Clinical and Biological Research, 336, 93-108.
Vandenbark AA, Hashim G, Offner H. Myelin Basic Protein, MHC Restriction Molecules and T Cell Repertoire. Prog Clin Biol Res. 1990;336:93-108. PubMed PMID: 1691512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myelin basic protein, MHC restriction molecules and T cell repertoire. AU - Vandenbark,A A, AU - Hashim,G, AU - Offner,H, PY - 1990/1/1/pubmed PY - 1990/1/1/medline PY - 1990/1/1/entrez SP - 93 EP - 108 JF - Progress in clinical and biological research JO - Prog Clin Biol Res VL - 336 N2 - 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. SN - 0361-7742 UR - https://www.unboundmedicine.com/medline/citation/1691512/Myelin_basic_protein_MHC_restriction_molecules_and_T_cell_repertoire_ L2 - https://antibodies.cancer.gov/detail/CPTC-HLA-C-1 DB - PRIME DP - Unbound Medicine ER -