T cell receptor (TCR)-derived peptides have been used to induce regulatory T cells which recognize T cells of specific elements and downregulate the autoimmune response. Consistent with these observations, priming of peptides corresponding to V beta 8 complementarity-determining region 2 (CDR2) was found to specifically suppress the proliferation of V beta 8+ T cells in the draining lymph nodes. Similarly, the generation of V beta 8-dominant T cell responses was prevented locally by vaccination with V beta 8 CDR2 peptides. There was a good correlation between the downregulation of V beta 8+ T cells and the inhibition of the corresponding T cell responses in different lymphoid tissues. No systemic inhibition could be detected even after an interval which would allow the redistribution of the "regulatory T cells." T cells specific for V beta 8 CDR2 peptides was generated following peptide immunization. However, the appearance of these TCR peptide-specific T cells was independent of the downregulation of V beta 8+ T cells. The transient and localized inhibitory effects of TCR-derived peptides indicate that these peptides have very limited use in regulating specific T cell response.