title: Diverse fine specificity and receptor repertoire of T cells reactive to the major VP1 epitope (VP1230-250) of Theiler's virus: V beta restriction correlates with T cell recognition of the c-terminal residue.
abstract: Theiler's murine encephalomyelitis virus induces chronic demyelinating disease in genetically susceptible mice. The histopathological and immunological manifestation of the disease closely resembles human multiple sclerosis, and, thus, this system serves as a relevant infectious model for multiple sclerosis. The pathogenesis of demyelination appears to be mediated by the inflammatory Th1 response to viral epitopes. In this study, T cell repertoire reactive to the major pathogenic VP1 epitope region (VP1233-250) was analyzed. Diverse minimal T cell epitopes were found within this region, and yet close to 50% of the VP1-reactive T cell hybridomas used V beta 16. The majority (8/11) of the V beta 16+ T cells required the C-terminal amino acid residue on the epitope, valine at position 245, and every T cell hybridoma recognizing this C-terminal residue expressed V beta 16. However, the complementarity-determining region 3 sequences of the V beta 16+ T cell hybridomas were markedly heterogeneous. In contrast, such a restriction was not found in the V alpha usage. Only restricted residues at this C-terminal position allowed for T cell activation, suggesting that V beta 16 may recognize this terminal residue. Further functional competition analysis for TCR and MHC class II-contacting residues indicate that many different residues can be involved in the class II and/or TCR binding depending on the T cell population, even if they recognize the identical minimal epitope region. Thus, recognition of the C-terminal residue of a minimal T cell epitope may associate with a particular V beta (but not V alpha) subfamily-specific sequence, resulting in a highly restricted V beta repertoire of the epitope-specific T cells.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA. bskim@nwu.edu
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
authors.forename: Y Y
authors.initials: YY
authors.lastname: Bahk
authors.forename: H K
authors.initials: HK
authors.lastname: Kang
authors.forename: R L
authors.initials: RL
authors.lastname: Yauch
authors.forename: J A
authors.initials: JA
authors.lastname: Kang
authors.forename: M J
authors.initials: MJ
authors.lastname: Park
authors.forename: N M
authors.initials: NM
authors.lastname: Ponzio
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002213:Capsid / Q000276:immunology* / Q000378:metabolism; D036022:Capsid Proteins; D017124:Conserved Sequence / Q000276:immunology; D006224:Cricetinae; D003711:Demyelinating Diseases / Q000209:etiology / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D017945:Theilovirus / Q000276:immunology*
chemical_list: D000596:Amino Acids; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C442551:VP1 protein, Theilovirus