Vaccination with a recombinant V alpha domain of a TCR prevents the development of collagen-induced arthritis

Autor: E F Rosloniec, D D Brand, K B Whittington, J M Stuart, M Ciubotaru, E S Ward
Rok vydání: 1995
Předmět:
Zdroj: The Journal of Immunology. 155:4504-4511
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.155.9.4504
Popis: 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.
Databáze: OpenAIRE