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Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes.
J Immunol. 1992 Mar 15; 148(6):1706-11.JI

Abstract

In Lewis rats, immunization with myelin basic protein induces two distinct encephalitogenic T cell populations, those responding to the immunodominant 72-89 epitope and those specific for a secondary epitope including residues 87-99. The 72-89 specific T cells were I-A restricted and preferentially expressed V beta 8.2 in their TCR. To determine the fine specificity, MHC restriction, and TCR V beta gene use in T cells reactive to the secondary epitope, we characterized 23 T cell clones from the lymph nodes (LN) and spinal cords (SC) of rats immunized with either whole basic protein or synthetic peptides S85-99 and S87-99 that were found to be functionally similar. The S85-99/S87-99 specific clones from LN and SC were all encephalitogenic despite differences in recognition of intact basic protein and class II MHC restriction. Unlike LN clones that overexpressed V beta 8 (46%+) and V beta 6 (31%+), however, SC clones were strongly biased (86%+) in their expression of V beta 6. This V gene bias raised the possibility of TCR peptide therapy using V beta 6 peptides. The V beta 6 sequence was similar to V beta 8.2 in the CDR2 region, and the corresponding peptides from this region were found to be cross-reactive in vivo. Moreover, both peptides were effective in the treatment of EAE induced with either S85-99, biased in V beta 6+ and V beta 8+ T cells, or guinea pig basic protein, biased only in V beta 8+ T cells. These data demonstrate the presence of common immunogenic epitopes among subsets of TCR V region gene families that possess important regulatory activity on effector T cell function.

Authors+Show Affiliations

Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OR 97201.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1371785

Citation

Offner, H, et al. "Characterization of the Immune Response to a Secondary Encephalitogenic Epitope of Basic Protein in Lewis Rats. I. T Cell Receptor Peptide Regulation of T Cell Clones Expressing Cross-reactive V Beta Genes." Journal of Immunology (Baltimore, Md. : 1950), vol. 148, no. 6, 1992, pp. 1706-11.
Offner H, Vainiene M, Gold DP, et al. Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes. J Immunol. 1992;148(6):1706-11.
Offner, H., Vainiene, M., Gold, D. P., Celnik, B., Wang, R., Hashim, G. A., & Vandenbark, A. A. (1992). Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes. Journal of Immunology (Baltimore, Md. : 1950), 148(6), 1706-11.
Offner H, et al. Characterization of the Immune Response to a Secondary Encephalitogenic Epitope of Basic Protein in Lewis Rats. I. T Cell Receptor Peptide Regulation of T Cell Clones Expressing Cross-reactive V Beta Genes. J Immunol. 1992 Mar 15;148(6):1706-11. PubMed PMID: 1371785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes. AU - Offner,H, AU - Vainiene,M, AU - Gold,D P, AU - Celnik,B, AU - Wang,R, AU - Hashim,G A, AU - Vandenbark,A A, PY - 1992/3/15/pubmed PY - 1992/3/15/medline PY - 1992/3/15/entrez SP - 1706 EP - 11 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 148 IS - 6 N2 - In Lewis rats, immunization with myelin basic protein induces two distinct encephalitogenic T cell populations, those responding to the immunodominant 72-89 epitope and those specific for a secondary epitope including residues 87-99. The 72-89 specific T cells were I-A restricted and preferentially expressed V beta 8.2 in their TCR. To determine the fine specificity, MHC restriction, and TCR V beta gene use in T cells reactive to the secondary epitope, we characterized 23 T cell clones from the lymph nodes (LN) and spinal cords (SC) of rats immunized with either whole basic protein or synthetic peptides S85-99 and S87-99 that were found to be functionally similar. The S85-99/S87-99 specific clones from LN and SC were all encephalitogenic despite differences in recognition of intact basic protein and class II MHC restriction. Unlike LN clones that overexpressed V beta 8 (46%+) and V beta 6 (31%+), however, SC clones were strongly biased (86%+) in their expression of V beta 6. This V gene bias raised the possibility of TCR peptide therapy using V beta 6 peptides. The V beta 6 sequence was similar to V beta 8.2 in the CDR2 region, and the corresponding peptides from this region were found to be cross-reactive in vivo. Moreover, both peptides were effective in the treatment of EAE induced with either S85-99, biased in V beta 6+ and V beta 8+ T cells, or guinea pig basic protein, biased only in V beta 8+ T cells. These data demonstrate the presence of common immunogenic epitopes among subsets of TCR V region gene families that possess important regulatory activity on effector T cell function. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1371785/Characterization_of_the_immune_response_to_a_secondary_encephalitogenic_epitope_of_basic_protein_in_Lewis_rats__I__T_cell_receptor_peptide_regulation_of_T_cell_clones_expressing_cross_reactive_V_beta_genes_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=1371785 DB - PRIME DP - Unbound Medicine ER -