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 (IL 2) and expression of IL 2 receptors were then assayed to examine any difference in stimulation between TT and SP. Both IL2 and IL2 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 IL2 released by the TT-sensitized CD4 cells to stimulate the SP-sensitized CD4 cells that produce inadequate amounts of IL2. Indeed, addition of recombinant IL2 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.
Department of Immunology, United Medical and Dental School, London, GB.
A
A
Childerstone
J A
JA
Haron
T
T
Lehner
D000942:Antigens, Bacterial / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002450:Cell Communication; D002469:Cell Separation; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013295:Streptococcus mutans / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D013745:Tetanus Toxoid / Q000276:immunology; D013936:Thymidine / Q000378:metabolism
D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D007376:Interleukin-2; D010455:Peptides; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D013936:Thymidine