Selection of anti-myelin basic protein T-cell lines in the lewis rat: V-beta 8.2 dominance and conserved complementarity-determining-region-3 motifs are dependent on serine at position 78 of myelin basic protein.
In the Lewis rat, the dominant T cell repertoire to myelin basic protein (MBP) is directed to the peptide 71-87 and the T cell receptors of pathogenic T cells are of the Vbeta 8.2 genotype with short CDR3 sequences having a characteristic motif. However, this paradigm has been reached through analysis of long-term encephalitogenic lines and clones. We initiated the present study to examine the process of selection of the TCR Vbeta 8.2 and characteristic CDR3 motifs upon immunization with guinea-pig MBP, and rat or guinea-pig 71-87 peptides. We found that the dominance of Vbeta 8.2 developed progressively over 4-6 in vitro stimulations. Following immunization with rat 70-86, which differs from the guinea-pig peptide in one amino acid at position 78, the dominance of Vbeta 8.2 and the characteristic CDR sequences are not seen. Thus, Vbeta 8.2 dominance and specific CDR3 TCR motifs are seen with heterologous GpMBP but not with self rat MBP.
Mor
F
F
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Kantorowitz
M
M
Cohen
I R
IR
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007135:Immunoglobulin Variable Region; D007376:Interleukin-2 / Q000494:pharmacology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D007135:Immunoglobulin Variable Region; D007376:Interleukin-2; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta