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T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis.
Clin Immunol 2004; 111(1):53-60CI

Abstract

Epitope spreading has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS). T cell epitope spreading has been demonstrated in rodents for myelin basic protein (MBP) and proteolipid protein (PLP) determinants, but not for myelin oligodendrocyte glycoprotein (MOG), another important myelin antigen. Moreover, the role of human autoimmunity-associated MHC molecules in epitope spreading, including HLA-DR2 and DR4, has not been formally examined. To address these questions, we investigated epitope spreading to MOG determinants in HLA-DR4 (DRB1*0401) transgenic mice during EAE. The data show that upon induction of EAE in HLA-DR4 transgenic mice with the immunodominant HLA-DR4-restricted MOG peptide 97-108 (MOG(97-108); TCFFRDHSYQEE), the T cell response diversifies over time to MOG(181-200) (core: MOG(183-191); FVIVPVLGP) and MBP. The spreading epitope MOG(181-200) binds with high affinity to HLA-DRB1*0401 and is presented by human HLA-DRB1*0401+antigen presenting cells. Moreover, this epitope is encephalitogenic in HLA-DRB1*0401 transgenic mice. This study demonstrates intra- and intermolecular epitope spreading to MOG and MBP in "humanized" HLA-DR4 transgenic mice.

Authors+Show Affiliations

Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.No affiliation info availableNo 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, P.H.S.

Language

eng

PubMed ID

15093552

Citation

Klehmet, Juliane, et al. "T Cell Epitope Spreading to Myelin Oligodendrocyte Glycoprotein in HLA-DR4 Transgenic Mice During Experimental Autoimmune Encephalomyelitis." Clinical Immunology (Orlando, Fla.), vol. 111, no. 1, 2004, pp. 53-60.
Klehmet J, Shive C, Guardia-Wolff R, et al. T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis. Clin Immunol. 2004;111(1):53-60.
Klehmet, J., Shive, C., Guardia-Wolff, R., Petersen, I., Spack, E. G., Boehm, B. O., ... Forsthuber, T. G. (2004). T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis. Clinical Immunology (Orlando, Fla.), 111(1), pp. 53-60.
Klehmet J, et al. T Cell Epitope Spreading to Myelin Oligodendrocyte Glycoprotein in HLA-DR4 Transgenic Mice During Experimental Autoimmune Encephalomyelitis. Clin Immunol. 2004;111(1):53-60. PubMed PMID: 15093552.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis. AU - Klehmet,Juliane, AU - Shive,Carey, AU - Guardia-Wolff,Rocio, AU - Petersen,Ines, AU - Spack,Edward G, AU - Boehm,Bernhard O, AU - Weissert,Robert, AU - Forsthuber,Thomas G, PY - 2003/07/11/received PY - 2003/12/30/accepted PY - 2004/4/20/pubmed PY - 2004/5/28/medline PY - 2004/4/20/entrez SP - 53 EP - 60 JF - Clinical immunology (Orlando, Fla.) JO - Clin. Immunol. VL - 111 IS - 1 N2 - Epitope spreading has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS). T cell epitope spreading has been demonstrated in rodents for myelin basic protein (MBP) and proteolipid protein (PLP) determinants, but not for myelin oligodendrocyte glycoprotein (MOG), another important myelin antigen. Moreover, the role of human autoimmunity-associated MHC molecules in epitope spreading, including HLA-DR2 and DR4, has not been formally examined. To address these questions, we investigated epitope spreading to MOG determinants in HLA-DR4 (DRB1*0401) transgenic mice during EAE. The data show that upon induction of EAE in HLA-DR4 transgenic mice with the immunodominant HLA-DR4-restricted MOG peptide 97-108 (MOG(97-108); TCFFRDHSYQEE), the T cell response diversifies over time to MOG(181-200) (core: MOG(183-191); FVIVPVLGP) and MBP. The spreading epitope MOG(181-200) binds with high affinity to HLA-DRB1*0401 and is presented by human HLA-DRB1*0401+antigen presenting cells. Moreover, this epitope is encephalitogenic in HLA-DRB1*0401 transgenic mice. This study demonstrates intra- and intermolecular epitope spreading to MOG and MBP in "humanized" HLA-DR4 transgenic mice. SN - 1521-6616 UR - https://www.unboundmedicine.com/medline/citation/15093552/T_cell_epitope_spreading_to_myelin_oligodendrocyte_glycoprotein_in_HLA_DR4_transgenic_mice_during_experimental_autoimmune_encephalomyelitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1521661604000051 DB - PRIME DP - Unbound Medicine ER -