TY - JOUR
T1 - T cell receptor peptides in treatment of autoimmune disease
T2 - Rationale and potential
AU - Vandenbark, A. A.
AU - Hashim, G. A.
AU - Offner, H.
PY - 1996
Y1 - 1996
N2 - The natural tendency in T cell-mediated autoimmune conditions to develop focused antigen-specific responses that over-utilize certain T cell receptor (TCR) V region segments prompts the induction of anti-TCR-specific T cells and antibodies that can inhibit the pathogenic T cells and promote recovery from disease. This natural regulatory network can be manipulated by injecting synthetic peptide vaccines that correspond to segments of the over-expressed V genes. In experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis (MS), the pathogenic T cells are directed at myelin components, including basic protein (MBP). In some strains such as the Lewis rat and the PL/J mouse, the encephalitogenic BP-specific T cells overexpress a particular V region gene (Vβ8.2) in their TCR. In vivo administration of Vβ8.2 peptides in rats or mice can prevent and treat EAE by boosting regulatory anti-Vβ8.2-specific T cells that inhibit but do not delete the encephalitogenic specificities. This regulation is mediated by soluble factors, suggesting that the presence of regulatory TCR-specific T cells within the target organ (the central nervous system) may inhibit not only the stimulating Vβ8.2+ T cells, but also bystander T cells bearing different V genes. Parallel studies in MS patients have revealed striking V gene biases among BP-specific T cell clones from some patients that provided a rationale for TCR peptide therapy. Injection of Vβ5.2 and Vβ6.1 peptides boosted the frequency of TCR peptide-specific T cells and reduced responses to BP, in some cases with clinical benefit, indicating the presence of an anti-TCR regulatory network in humans that may also be manipulated with TCR peptide therapy.
AB - The natural tendency in T cell-mediated autoimmune conditions to develop focused antigen-specific responses that over-utilize certain T cell receptor (TCR) V region segments prompts the induction of anti-TCR-specific T cells and antibodies that can inhibit the pathogenic T cells and promote recovery from disease. This natural regulatory network can be manipulated by injecting synthetic peptide vaccines that correspond to segments of the over-expressed V genes. In experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis (MS), the pathogenic T cells are directed at myelin components, including basic protein (MBP). In some strains such as the Lewis rat and the PL/J mouse, the encephalitogenic BP-specific T cells overexpress a particular V region gene (Vβ8.2) in their TCR. In vivo administration of Vβ8.2 peptides in rats or mice can prevent and treat EAE by boosting regulatory anti-Vβ8.2-specific T cells that inhibit but do not delete the encephalitogenic specificities. This regulation is mediated by soluble factors, suggesting that the presence of regulatory TCR-specific T cells within the target organ (the central nervous system) may inhibit not only the stimulating Vβ8.2+ T cells, but also bystander T cells bearing different V genes. Parallel studies in MS patients have revealed striking V gene biases among BP-specific T cell clones from some patients that provided a rationale for TCR peptide therapy. Injection of Vβ5.2 and Vβ6.1 peptides boosted the frequency of TCR peptide-specific T cells and reduced responses to BP, in some cases with clinical benefit, indicating the presence of an anti-TCR regulatory network in humans that may also be manipulated with TCR peptide therapy.
KW - EAE
KW - MS
KW - TCR
UR - http://www.scopus.com/inward/record.url?scp=0029930328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029930328&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-4547(19960215)43:4<391::AID-JNR1>3.0.CO;2-A
DO - 10.1002/(SICI)1097-4547(19960215)43:4<391::AID-JNR1>3.0.CO;2-A
M3 - Short survey
C2 - 8699526
AN - SCOPUS:0029930328
SN - 0360-4012
VL - 43
SP - 391
EP - 402
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 4
ER -