A cross-reactive idiotope on T cells from PL/J mice and Lewis rats that recognizes different myelin basic protein encephalitogenic epitopes but is restricted by TCR V beta 8.2.
Encephalitogenic T cells of both PL/J mice and Lewis rats are restricted by TCR V beta 8.2, although they recognize different epitopes in the myelin basic protein (MBP) molecule. We sought the presence of a cross-reactive idiotope (Id) in encephalitogenic T cells of Lewis rats by examining the effects of mAb F30 anti-Id, which recognized a TCR Id in PL/J T cells, on the encephalitogenic LR88L1 cell line derived from Lewis rats and specific for guinea pig MBP peptide 68-88. The LR88L1 cells were I-A restricted and TCR V beta 8.2+, and their proliferation and secretion of IL-2 and TNF-alpha induced by guinea pig MBP peptide 68-88 was inhibited by mAb F30 anti-Id. As shown by FACS analysis and by immunoprecipitation of TCR from radiolabeled LR88L1 cell lysates, the F30 anti-Id bound to the TCRs of V beta 8.2+ LR88L1 cells. In addition, TCR sequences in the F30+ population of LR88L1 cells were the same as those of encephalitogenic Lewis rat T cells published previously. The F30+ LR88L1 cells showed reduced encephalitogenicity compared with F30- or unsorted LR88L1 cells. The mechanism for this reduction by anti-Id probably resulted from the induction of anergy, in that IL-2 reversed the anti-Id effect. The control LR99L1 T cell line, also encephalitogenic, but specific for MBP peptide 87-99 and I-E, and not TCR V beta 8.2 restricted, failed to react with, or have its cytokine secretion inhibited by, mAb F30 anti-Id. These results demonstrate an interspecies cross-reactive Id expressed in common by encephalitogenic T cells that share a similar TCR, although they differ in MBP epitope specificity. These findings suggest that a common Id restricted by TCR, but less restricted by the encephalitogenic epitope, and recognized by the Id-bearing autoreactive T cells may represent an immunotherapeutic approach for treating autoimmune demyelinating diseases.
Zhou
S R
SR
Department of Neurology, University of Alabama at Birmingham 35294.
Whitaker
J N
JN
Han
Q
Q
Maier
C
C
Blalock
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D003429:Cross Reactions; D017931:DNA Primers / Q000737:chemistry; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha