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T cell interactions generated by synthetic peptides covalently linked to a carrier

We have attempted to extend the synthetic peptide‐carrier bridge concept of T cell‐B cell interaction to T cell‐T cell interaction. DNA synthesis of human CD4 cells that were sensitized in vivo to a native streptococcal antigen (SA) was stimulated in vitro with synthetic peptides (SP) derived from the sequence of native SA. The SP were linked to tetanus toxoid (TT) as a carrier which was recognized by primed T cells. The uptake of [3H]thymidine was significantly greater when stimulated with covalently linked SP‐TT than that with non‐covalently mixed SP and TT. The TT‐ and SP‐sensitized CD4 cells were then enriched and depleted by panning on TT‐ or SP‐treated monocyte layers. When TT‐enriched CD4 cells were reconstituted with SP‐enriched cells, [3H]thymidine uptake was significantly greater with the linked SP‐TT than with the mixed SP and TT. However, reconstitution of the TT‐enriched with SP‐depleted CD4 cells or the converse failed to increase significantly DNA synthesis by cells stimulated with the linked SP‐TT. The production of interleukin 2 (IL2) and expression of IL2 receptors were then assayed to examine any difference in stimulation between TT and SP. Both IL 2 and IL 2 receptors were diminished and delayed when T cells were stimulated with SP as compared with TT. The results suggest that epitope‐linked clusters of monocytes, TT‐sensitized CD4 and SP‐sensitized CD4 cells enable IL 2 released by the TT‐sensitized CD4 cells to stimulate the SP‐sensitized CD4 cells that produce inadequate amounts of IL 2. Indeed, addition of recombinant IL 2 to T cells stimulated with mixed SP and TT induces an increase in DNA synthesis which becomes similar to that resulting from stimulation with the linked SP‐TT.