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Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG): prime role of MOG44F in selection and control of MOG-reactive T cells in H-2b mice.
Eur J Immunol. 2006 Feb; 36(2):478-93.EJ

Abstract

Myelin oligodendrocyte glycoprotein (MOG) is an important myelin target antigen, and MOG-induced EAE is now a widely used model for multiple sclerosis. Clonal dissection revealed that MOG-induced EAE in H-2(b) mice is associated with activation of an unexpectedly large number of T cell clones reactive against the encephalitogenic epitope MOG35-55. These clones expressed extremely diverse TCR with no obvious CDR3alpha/CDR3beta motif(s). Despite extensive TCR diversity, the cells required MOG40-48 as their common core epitope and shared MOG44F as their major TCR contact. Fine epitope-specificity analysis with progressively truncated peptides suggested that the extensive TCR heterogeneity is mostly related to differential recognition of multiple overlapping epitopes nested within MOG37-52, each comprised of a MOG40-48 core flanked at the N- and/or the C-terminus by a variable number of residues important for interaction with different TCR. Abrogation of both the encephalitogenic potential of MOG and T cell reactivity against MOG by a single mutation (MOG44F/MOG44A), together with effective down-regulation of MOG-induced EAE by MOG37-44A-52, confirmed in vivo the primary role for MOG44F in the selection/activation of MOG-reactive T cells. We suggest that such a highly focused T cell autoreactivity could be a selective force that offsets the extensive TCR diversity to facilitate a more "centralized control" of pathogenic MOG-related T cell autoimmunity.

Authors+Show Affiliations

Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. avraham.ben-nun@weizmann.ac.ilNo 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

Language

eng

PubMed ID

16453383

Citation

Ben-Nun, Avraham, et al. "Anatomy of T Cell Autoimmunity to Myelin Oligodendrocyte Glycoprotein (MOG): Prime Role of MOG44F in Selection and Control of MOG-reactive T Cells in H-2b Mice." European Journal of Immunology, vol. 36, no. 2, 2006, pp. 478-93.
Ben-Nun A, Kerlero de Rosbo N, Kaushansky N, et al. Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG): prime role of MOG44F in selection and control of MOG-reactive T cells in H-2b mice. Eur J Immunol. 2006;36(2):478-93.
Ben-Nun, A., Kerlero de Rosbo, N., Kaushansky, N., Eisenstein, M., Cohen, L., Kaye, J. F., & Mendel, I. (2006). Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG): prime role of MOG44F in selection and control of MOG-reactive T cells in H-2b mice. European Journal of Immunology, 36(2), 478-93.
Ben-Nun A, et al. Anatomy of T Cell Autoimmunity to Myelin Oligodendrocyte Glycoprotein (MOG): Prime Role of MOG44F in Selection and Control of MOG-reactive T Cells in H-2b Mice. Eur J Immunol. 2006;36(2):478-93. PubMed PMID: 16453383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG): prime role of MOG44F in selection and control of MOG-reactive T cells in H-2b mice. AU - Ben-Nun,Avraham, AU - Kerlero de Rosbo,Nicole, AU - Kaushansky,Nathali, AU - Eisenstein,Miriam, AU - Cohen,Lydia, AU - Kaye,Joel F, AU - Mendel,Itzhack, PY - 2006/2/3/pubmed PY - 2006/3/25/medline PY - 2006/2/3/entrez SP - 478 EP - 93 JF - European journal of immunology JO - Eur J Immunol VL - 36 IS - 2 N2 - Myelin oligodendrocyte glycoprotein (MOG) is an important myelin target antigen, and MOG-induced EAE is now a widely used model for multiple sclerosis. Clonal dissection revealed that MOG-induced EAE in H-2(b) mice is associated with activation of an unexpectedly large number of T cell clones reactive against the encephalitogenic epitope MOG35-55. These clones expressed extremely diverse TCR with no obvious CDR3alpha/CDR3beta motif(s). Despite extensive TCR diversity, the cells required MOG40-48 as their common core epitope and shared MOG44F as their major TCR contact. Fine epitope-specificity analysis with progressively truncated peptides suggested that the extensive TCR heterogeneity is mostly related to differential recognition of multiple overlapping epitopes nested within MOG37-52, each comprised of a MOG40-48 core flanked at the N- and/or the C-terminus by a variable number of residues important for interaction with different TCR. Abrogation of both the encephalitogenic potential of MOG and T cell reactivity against MOG by a single mutation (MOG44F/MOG44A), together with effective down-regulation of MOG-induced EAE by MOG37-44A-52, confirmed in vivo the primary role for MOG44F in the selection/activation of MOG-reactive T cells. We suggest that such a highly focused T cell autoreactivity could be a selective force that offsets the extensive TCR diversity to facilitate a more "centralized control" of pathogenic MOG-related T cell autoimmunity. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/16453383/Anatomy_of_T_cell_autoimmunity_to_myelin_oligodendrocyte_glycoprotein__MOG_:_prime_role_of_MOG44F_in_selection_and_control_of_MOG_reactive_T_cells_in_H_2b_mice_ DB - PRIME DP - Unbound Medicine ER -