Monoclonal antibodies to a TCR idiotope modulate the superantigen-induced responses of encephalitogenic rat T cells.
Superantigens, such as staphylococcal enterotoxins, activate T lymphocytes by linking MHC class II molecules on antigen presenting cells to the V beta element of the TCR. Through this effect on T cells, superantigens may influence the immune response and autoimmune disease. In fact, superantigens may activate or anergize cells involved in the production of experimental allergic encephalomyelitis. Lewis rats recognize an encephalitogenic epitope in myelin basic protein (MBP) residues 68-88 through an MHC class II I-A restricted process using TCR V beta 8.2. The F30 murine mAb reacts with an encephalitogenic idiotope (Id) on the TCR of V beta 8.2+ encephalitogenic Lewis rat T cells. In the present study it was demonstrated that the same mAb anti-Id inhibited the proliferation and IL-2 secretion induced by staphylococcal enterotoxins A, B and E in a V beta 8.2+ encephalitogenic Lewis rat T cell line specific for guinea pig MBP peptide 68-88. The mAb anti-Id did not inhibit the response of control T cells similarly derived but inhibited V beta 8.2- and recognizing MBP peptide 87-99. Control anti-Id failed to inhibit the response of either cell line. These findings imply that the specific antigen and superantigen react with TCR in a manner similar enough to be inhibited by the same anti-Id. The mechanism may involve the induction of anergy by the anti-Id, interference/steric hindrance by the reaction of anti-Id with TCR and possibly a little direct reaction of anti-Id with superantigens. Anti-Id directed immunotherapy may have a role in modulating the damage of inflammatory demyelination induced by both specific antigens and superantigens.
Zhou
S R
SR
Department of Neurology, University of Alabama at Birmingham 35294-0007.
DeSilva
T S
TS
Han
Q
Q
Whitaker
J N
JN
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha