TY - JOUR
T1 - Antagonism of superantigen-stimulated helper T-cell clones and hybridomas by altered peptide ligand
AU - Evavold, Brian D.
AU - Sloan-Lancaster, Joanne
AU - Allen, Paul M.
PY - 1994/3/15
Y1 - 1994/3/15
N2 - T-cell activation by an immunogenic peptide can be antagonized by nonstimulatory analogs of that peptide. We investigated this T-cell receptor antagonism by using staphylococcal enterotoxin superantigen to stimulate hemoglobin-specific helper T (T(h)) cells because its activation pathway may differ from that of conventional antigen. Interestingly, superantigen activation of these T(h) cells was antagonized by hemoglobin peptide analogs even though agonist (superantigen) and antagonist (analog peptide) bind at different sites on the major histocompatibility complex-encoded molecule and the T-cell receptor. The antagonism appeared to be a fundamental block in T- cell activation, as phosphoinositol generation, cytokine production, and proliferation were reduced in T(h1) clones, and, similarly, proliferative and cytokine responses were inhibited in T(h2) cells. Even T-cell hybridoma activation (cytokine production and apoptosis) was inhibited by peptide antagonists. Furthermore, analog peptides that functioned as partial agonists for these T(h) cells also antagonized superantigen-induced proliferation and thus were a subset of the peptide antagonists. In summary, our results demonstrate that analogs of immunogenic peptide are potent antagonists for T(h) cell responses induced by superantigen as well as immunogenic peptide.
AB - T-cell activation by an immunogenic peptide can be antagonized by nonstimulatory analogs of that peptide. We investigated this T-cell receptor antagonism by using staphylococcal enterotoxin superantigen to stimulate hemoglobin-specific helper T (T(h)) cells because its activation pathway may differ from that of conventional antigen. Interestingly, superantigen activation of these T(h) cells was antagonized by hemoglobin peptide analogs even though agonist (superantigen) and antagonist (analog peptide) bind at different sites on the major histocompatibility complex-encoded molecule and the T-cell receptor. The antagonism appeared to be a fundamental block in T- cell activation, as phosphoinositol generation, cytokine production, and proliferation were reduced in T(h1) clones, and, similarly, proliferative and cytokine responses were inhibited in T(h2) cells. Even T-cell hybridoma activation (cytokine production and apoptosis) was inhibited by peptide antagonists. Furthermore, analog peptides that functioned as partial agonists for these T(h) cells also antagonized superantigen-induced proliferation and thus were a subset of the peptide antagonists. In summary, our results demonstrate that analogs of immunogenic peptide are potent antagonists for T(h) cell responses induced by superantigen as well as immunogenic peptide.
UR - http://www.scopus.com/inward/record.url?scp=0028289311&partnerID=8YFLogxK
U2 - 10.1073/pnas.91.6.2300
DO - 10.1073/pnas.91.6.2300
M3 - Article
C2 - 8134391
AN - SCOPUS:0028289311
SN - 0027-8424
VL - 91
SP - 2300
EP - 2304
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -