The Fine Specificity of Regulatory T Cells

We have demonstrated the induction of suppressor T cells of highly restricted specificity in a nonresponder strain. HEL (hen egg-white lysozyme) fails to elicit an antibody response in C57BL/10 (B10) mice whereas the closely related REL (ring-necked pheasant egg-white lysozyme) is strongly immunogenic. However, an anti-HEL primary antibody response can be obtained in B10 mice in vivo or in vitro by coupling HEL to red blood cells (RBC). Preimmunization with HEL-CFA induced reduction of the anti-HEL PFC response to a subsequent challenge with HEL-RBC. Suppression was demonstrated by in vitro mixing experiments and was mediated with remarkable efficiency by I-J positive suppressor T cells. Suppression was specific for the anti-HEL response and did not affect the anti-RBC response. Both IgM and IgG anti-HEL in vivo antibody responses showed 70 to 80% suppression. Relatively high doses of antigen were required to generate efficient suppression. Optimal suppression was reached within 4 weeks after HEL priming and remained maximal at least 9 weeks after priming. Fine specificity in the expression of suppressive activity was displayed by HEL-specific suppressor cells that were not able to suppress an anti-REL response. Furthermore, REL priming did not suppress an in vitro anti-HEL response to HEL-RBC. The close similarity in amino acid sequence and in B cell cross-reactivity between HEL and REL, contrasted with the lack of REL recognition by HEL-specific suppressor T cells, indicates that a limited region on the nonimmunogenic HEL, absent on REL, can account for the induction of suppression.