Vaccination with a recombinant V alpha domain of a TCR prevents the development of collagen-induced arthritis.
A recombinant TCR domain, derived from a T cell hybridoma that recognizes an immunodominant type II collagen epitope, was used to vaccinate against collagen-induced arthritis in DBA/1 (H-2q) mice. The recombinant TCR domain comprises VA11.1-JA17 gene segments and is representative of the V alpha domains expressed by oligoclonal T cells in this disease model. Vaccination of mice 28 days before type II collagen (CII) immunization with this V alpha 11.1 domain resulted in a significantly decreased incidence of arthritis in DBA/1 mice, in contrast to vaccination with a V alpha 4-J alpha 40 domain derived from an encephalitogenic T cell hybridoma specific for MBP. Disease blockade is accompanied by a reduction in T and B cell responses to both the immunogen bovine CII and the autoantigen murine CII. V alpha 4 and V alpha 11.1 domains were found to be highly immunogenic in DBA/1 mice, inducing both T cell proliferation and the production of V alpha specific Abs, indicating that the vaccination effect of V alpha 11.1 is specific. This is the first report of V alpha-directed immunotherapy in an autoimmune disease model and demonstrates the potential use of recombinant TCR vaccines in the treatment of autoimmune diseases that involve oligoclonal autoreactive T cells.
Rosloniec
E F
EF
Veterans Affairs Medical Center, Memphis, TN 38104, USA.
Brand
D D
DD
Whittington
K B
KB
Stuart
J M
JM
Ciubotaru
M
M
Ward
E S
ES
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001168:Arthritis / Q000139:chemically induced / Q000517:prevention & control*; D001483:Base Sequence; D002417:Cattle; D003094:Collagen / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000627:therapeutic use
D016693:Receptors, Antigen, T-Cell, alpha-beta; D014614:Vaccines, Synthetic; D003094:Collagen