Peptide antagonists inhibit proliferation and the production of IL-4 and/or IFN-gamma in T helper 1, T helper 2, and T helper 0 clones bearing the same TCR.
Engagement of a TCR by its peptide Ag bound by MHC class II molecules leads to T cell activation, resulting in proliferation and cytokine production. This agonist response can be antagonized by analogue peptides containing single amino acid substitutions. We used T cell clones isolated from a mouse transgenic for the rearranged TCR alpha- and beta-chains of the D10.G4.1 (D10) Th2 clone specific for hen egg conalbumin peptide 134-146 (CA 134-146) to characterize antagonist peptides for the D10.TCR. The D10.TCR CD4 T cell clones proliferated in a dose-dependent manner to CA 134-146, and this proliferation was accompanied by secretion of IL-4 and/or IFN-gamma with Th1, Th2, and Th0 patterns. Proliferation of the clones was inhibited completely by CA 134-146 analogue peptides containing a substitution of the glutamic acid at position 8 with alanine (E8A) or threonine (E8T). The E8A and E8T peptides also antagonized the production of mRNA and subsequent cytokine secretion of IFN-gamma and/or IL-4. Our results, showing that antagonist peptides can inhibit both T cell proliferation and cytokine production in Th1, Th2, and Th0 clones all bearing the same TCR, demonstrate that the TCR:peptide interaction determines the outcome regardless of the phenotype of the clone. Thus, antagonism by peptides acts through the TCR.
Dittel
B N
BN
Section of Immunobiology, Yale University School of Medicine, and Howard Hughes Medical Institute, New Haven, CT 06510, USA.
Sant'Angelo
D B
DB
Janeway
C A
CA
D000818:Animals; D002455:Cell Division; D003207:Conalbumin / Q000737:chemistry / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D010455:Peptides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D003207:Conalbumin; D015847:Interleukin-4; D007371:Interferon-gamma