title: T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice.
abstract: Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced in laboratory animals by immunization with the major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the role of the T cell receptor (TCR) repertoire in susceptibility to EAE induced by these two autoantigens. Autoreactive T cells induced after immunization with MBP use a limited set of TCR. In contrast, we demonstrate that T cell clones that recognize the encephalitogenic PLP epitope (PLP 139-151) use diverse TCR genes. When the TCR repertoire is limited by introduction of a novel rearranged TCR V beta 8.2 chain in transgenic SJL mice, EAE could be induced in the transgenic mice by immunization with the encephalitogenic epitopes of PLP, but not with the encephalitogenic epitope of MBP. Thus, skewing the TCR repertoire affects the susceptibility to EAE by immunization with MBP but not with PLP. These data demonstrate the biological consequences of the usage of a more diverse T cell repertoire in the development of an autoimmune disease.
authors.affiliation: Center for Neurological Diseases, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: V K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: M
authors.initials: M
authors.lastname: Collins
authors.forename: A
authors.initials: A
authors.lastname: al-Sabbagh
authors.forename: R A
authors.initials: RA
authors.lastname: Sobel
authors.forename: M J
authors.initials: MJ
authors.lastname: Whitters
authors.forename: S S
authors.initials: SS
authors.lastname: Zamvil
authors.forename: M E
authors.initials: ME
authors.lastname: Dorf
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
authors.forename: H L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA