TY - JOUR
T1 - Degenerate antigen recognition by CD4+ effector T cells in experimental autoimmune encephalomyelitis
AU - McRae, Bradford L.
AU - Karandikar, Nitin J.
AU - Miller, Stephen D.
N1 - Funding Information:
Supported in part by USPHS NIH Grants NS30871 and NS26543.
PY - 1997/5
Y1 - 1997/5
N2 - Peptide-specific tolerance with PLP139-151 peptide analogs was used to compare the fine antigen-specificity requirements at both the inductive and effector phases of relapsing EAE (R-EAE). A PLP139-151 analog peptide containing a single substitution at the primary T cell receptor (TcR) contact residue (A144) did not induce proliferation in PLP139-151-primed CD4+ T cells. In addition, tolerance induced with ECDI-treated, A144-coupled splenocytes failed to prevent the inductive phase of PLP139-151-induced R-EAE or to inhibit the induction of peptide-specific DTH indicating that naive PLP139-151-specific T cells do not react with the A144 peptide analog. In contrast, A144-coupled splenocytes did prevent the expression of the effector phase of R-EAE and inhibited the elicitation of peptide-specific DTH responses upon administration to mice seven days after immunization with PLP139-151. The results provide in vivo evidence that 'antigen-experienced' T cells recognize a broader repertoire of antigens than do naive T cells and have important implications for the regulation of immune responses and for advancing our understanding of the pathogenesis and treatment of autoimmune disease.
AB - Peptide-specific tolerance with PLP139-151 peptide analogs was used to compare the fine antigen-specificity requirements at both the inductive and effector phases of relapsing EAE (R-EAE). A PLP139-151 analog peptide containing a single substitution at the primary T cell receptor (TcR) contact residue (A144) did not induce proliferation in PLP139-151-primed CD4+ T cells. In addition, tolerance induced with ECDI-treated, A144-coupled splenocytes failed to prevent the inductive phase of PLP139-151-induced R-EAE or to inhibit the induction of peptide-specific DTH indicating that naive PLP139-151-specific T cells do not react with the A144 peptide analog. In contrast, A144-coupled splenocytes did prevent the expression of the effector phase of R-EAE and inhibited the elicitation of peptide-specific DTH responses upon administration to mice seven days after immunization with PLP139-151. The results provide in vivo evidence that 'antigen-experienced' T cells recognize a broader repertoire of antigens than do naive T cells and have important implications for the regulation of immune responses and for advancing our understanding of the pathogenesis and treatment of autoimmune disease.
KW - SJL/J mice
KW - altered peptide ligands
KW - cytokines
KW - encephalitogenic peptide
KW - experimental autoimmune encephalomyelitis
KW - proteolipid protein
UR - http://www.scopus.com/inward/record.url?scp=0030894063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030894063&partnerID=8YFLogxK
U2 - 10.1016/S0165-5728(97)00014-3
DO - 10.1016/S0165-5728(97)00014-3
M3 - Article
C2 - 9143249
AN - SCOPUS:0030894063
SN - 0165-5728
VL - 75
SP - 156
EP - 162
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -