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CD8 T cell responses to myelin oligodendrocyte glycoprotein-derived peptides in humanized HLA-A*0201-transgenic mice.
J Immunol 2007; 179(8):5090-8JI

Abstract

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS. Though originally believed to be CD4-mediated, additional immune effector mechanisms, including myelin-specific CD8(+) T cells, are now proposed to participate in the pathophysiology of MS. To study the immunologic and encephalitogenic behavior of HLA-A*0201-binding myelin-derived epitopes in vivo, we used a humanized HLA-A*0201-transgenic mouse model. Eight HLA-A*0201-binding peptides derived from myelin oligodendrocyte glycoprotein (MOG), an immunodominant myelin self-Ag, were identified in silico. After establishing their relative affinity for HLA-A*0201 and their capacity to form stable complexes with HLA-A*0201 in vitro, their immunological characteristics were studied in HLA-A*0201-transgenic mice. Five MOG peptides, which bound stably to HLA-A*0201 exhibited strong immunogenicity by inducing a sizeable MOG-specific HLA-A*0201-restricted CD8(+) T cell response in vivo. Of these five candidate epitopes, four were processed by MOG-transfected RMA target cells and two peptides proved immunodominant in vivo in response to a plasmid-encoding native full-length MOG. One of the immunodominant MOG peptides (MOG(181)) generated a cytotoxic CD8(+) T cell response able to aggravate CD4(+)-mediated EAE. Therefore, this detailed in vivo characterization provides a hierarchy of candidate epitopes for MOG-specific CD8(+) T cell responses in HLA-A*0201 MS patients identifying the encephalitogenic MOG(181) epitope as a primary candidate.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale, Unité 563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.No affiliation info availableNo 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

Language

eng

PubMed ID

17911594

Citation

Mars, Lennart T., et al. "CD8 T Cell Responses to Myelin Oligodendrocyte Glycoprotein-derived Peptides in Humanized HLA-A*0201-transgenic Mice." Journal of Immunology (Baltimore, Md. : 1950), vol. 179, no. 8, 2007, pp. 5090-8.
Mars LT, Bauer J, Gross DA, et al. CD8 T cell responses to myelin oligodendrocyte glycoprotein-derived peptides in humanized HLA-A*0201-transgenic mice. J Immunol. 2007;179(8):5090-8.
Mars, L. T., Bauer, J., Gross, D. A., Bucciarelli, F., Firat, H., Hudrisier, D., ... Liblau, R. S. (2007). CD8 T cell responses to myelin oligodendrocyte glycoprotein-derived peptides in humanized HLA-A*0201-transgenic mice. Journal of Immunology (Baltimore, Md. : 1950), 179(8), pp. 5090-8.
Mars LT, et al. CD8 T Cell Responses to Myelin Oligodendrocyte Glycoprotein-derived Peptides in Humanized HLA-A*0201-transgenic Mice. J Immunol. 2007 Oct 15;179(8):5090-8. PubMed PMID: 17911594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD8 T cell responses to myelin oligodendrocyte glycoprotein-derived peptides in humanized HLA-A*0201-transgenic mice. AU - Mars,Lennart T, AU - Bauer,Jan, AU - Gross,David A, AU - Bucciarelli,Florence, AU - Firat,Huseyin, AU - Hudrisier,Denis, AU - Lemonnier,François, AU - Kosmatopoulos,Kostas, AU - Liblau,Roland S, PY - 2007/10/4/pubmed PY - 2007/12/6/medline PY - 2007/10/4/entrez SP - 5090 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 179 IS - 8 N2 - Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS. Though originally believed to be CD4-mediated, additional immune effector mechanisms, including myelin-specific CD8(+) T cells, are now proposed to participate in the pathophysiology of MS. To study the immunologic and encephalitogenic behavior of HLA-A*0201-binding myelin-derived epitopes in vivo, we used a humanized HLA-A*0201-transgenic mouse model. Eight HLA-A*0201-binding peptides derived from myelin oligodendrocyte glycoprotein (MOG), an immunodominant myelin self-Ag, were identified in silico. After establishing their relative affinity for HLA-A*0201 and their capacity to form stable complexes with HLA-A*0201 in vitro, their immunological characteristics were studied in HLA-A*0201-transgenic mice. Five MOG peptides, which bound stably to HLA-A*0201 exhibited strong immunogenicity by inducing a sizeable MOG-specific HLA-A*0201-restricted CD8(+) T cell response in vivo. Of these five candidate epitopes, four were processed by MOG-transfected RMA target cells and two peptides proved immunodominant in vivo in response to a plasmid-encoding native full-length MOG. One of the immunodominant MOG peptides (MOG(181)) generated a cytotoxic CD8(+) T cell response able to aggravate CD4(+)-mediated EAE. Therefore, this detailed in vivo characterization provides a hierarchy of candidate epitopes for MOG-specific CD8(+) T cell responses in HLA-A*0201 MS patients identifying the encephalitogenic MOG(181) epitope as a primary candidate. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/17911594/CD8_T_cell_responses_to_myelin_oligodendrocyte_glycoprotein_derived_peptides_in_humanized_HLA_A_0201_transgenic_mice_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=17911594 DB - PRIME DP - Unbound Medicine ER -