Induction of myelin basic protein-specific experimental autoimmune encephalomyelitis in C57BL/6 mice: mapping of T cell epitopes and T cell receptor V beta gene segment usage.
Early studies of murine experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP) divide various mouse strains into either "susceptible" or "resistant" phenotypes. Resistance is defined as lack of encephalitogenic responses after active immunization or adoptive transfer. It is now becoming clear that this unresponsiveness is not due to the inability of T cells to recognize MBP in the context of major histocompatibility complex (MHC) gene products. Using various manipulations, many laboratories are able to induce severe EAE in these strains. We previously reported that a combination of adoptive transfer and subsequent challenge of the recipients with MBP could overcome the resistance in many mouse strains (Shaw et al.: J Neuroimmunol 39:139-150, 1992). This approach now enables us to identify the encephalitogenic epitope and T cell receptor V beta usage in a prototype strain, C57BL/6 (B6). Pepsin-digested MBP fragments first located a major T cell epitope in a polypeptide containing residues 44-88. Overlapping synthetic peptides narrowed this epitope to p60-80. Truncated peptides from the carboxyl- or amino-terminus further mapped a minimal peptide to p67-76. This encephalitogenic epitope appears to be unique to B6 mice. Independent encephalitogenic T cell clones specific for this epitope were also generated. Of six such clones analyzed, five different TCR V beta's were found. Whether unbiased usage of encephalitogenic TCR V beta gene segments in B6 mice is related to its EAE resistant phenotype is not clear at this point.
Department of Immunology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
M K
MK
Shaw
C
C
Kim
H W
HW
Hao
F
F
Chen
H Y
HY
Tse
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced*; D018604:Epitope Mapping; D005260:Female; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein; D010434:Pepsin A; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010434:Pepsin A