Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.
Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin-specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance.
Falcioni
F
F
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Dembic
Z
Z
Muller
S
S
Lehmann
P V
PV
Nagy
Z A
ZA
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D004261:DNA Replication; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015342:DNA Probes; D007328:Insulin; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell; D004247:DNA