Experimental autoimmune encephalomyelitis-resistant mice have highly encephalitogenic myelin basic protein (MBP)-specific T cell clones that recognize a MBP peptide with high affinity for MHC class II.
BALB/c mice are resistant to disease induction when experimental protocols that induce experimental autoimmune encephalomyelitis (EAE) in susceptible strains of animals are used. We have previously described a panel of myelin basic protein (MBP)-specific CD4+ T cell clones from BALB/c mice, two of which induce moderate EAE when transferred to syngeneic recipients. These clones are I-E(d) restricted and recognize residues 151-160 of mouse MBP. Here, we describe a series of 17 MBP-reactive T cell clones, which were derived from two BALB/c mice. All are I-A(d) restricted and recognize nested epitopes in peptide 59-76 of mouse MBP. Four different TCR V beta chains are used by this panel of clones; these include V beta 8.2 (10/17), V beta 8.1 (2/17), V beta 7 (3/17), and V beta 14 (2/17). Twelve of fourteen clones tested adoptively transferred severe demyelinating EAE to syngeneic recipients. Studies of relative binding affinities of MBP peptides to class II molecules I-A(d) and I-E(d) show that peptide 59-76 binds with extremely high affinity to I-A(d), whereas three peptides that contains residues 151-160 bind poorly to I-E(d). These results are consistent with a growing number of reports that show that high affinity binding to class II is required for autoantigenic stimulation. Despite encephalitogenicity of 59-76-reactive T cells, active immunization of BALB/c mice with peptide 59-76 in adjuvant failed to induce either clinical or histologic signs of EAE. The implications of these findings for mechanisms of genetically determined EAE resistance are discussed.
Abromson-Leeman
S
S
Department of Pathology, Harvard Medical School, Boston, MA 02115.
Alexander
J
J
Bronson
R
R
Carroll
J
J
Southwood
S
S
Dorf
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002999:Clone Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology* / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D014611:Vaccination
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta