Usage of T cell receptor beta-chain variable gene is highly restricted at the site of inflammation in murine autoimmune uveitis.
Improved molecular methods allow identification of the specific autoaggressive T cells involved in autoimmune inflammations. In this study of interphotoreceptor retinoid-binding protein-induced uveitis, TCR V beta usage was studied using RNA-polymerase chain reaction amplification of transcripts derived directly from ocular tissues and from T cell lines obtained from the spleen. Specific V beta 5' primers from the major murine TCR V beta families were coupled with a common 3' primer from the V beta C region. Amplification of rearranged TCR V beta-D beta-J beta-C beta sequences was confirmed by Southern blot analysis. In ocular tissue from sensitized mice, TCR V beta expression was limited mainly to one to three V beta families, with predominant expression of V beta 2, V beta 12, and V beta 15. In most animals there was similar, albeit limited, TCR gene usage in both the recognition of autoantigen in uveitogenic T cell lines and at the site of inflammation in the eye. Identification of a limited TCR V beta repertoire in Ag-reactive T cell lines correlated with TCR usage at the target site of autoimmune expression. The gene products of the restricted TCR V beta rearrangements found in lesions and in the cell lines may serve as the target for selective immunotherapy.
Rao
N A
NA
Doheny Eye Institute, Los Angeles, CA 90033.
Naidu
Y M
YM
Bell
R
R
Lindsey
J W
JW
Pararajasegaram
G
G
Sun
Y
Y
Steinman
L
L
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D014605:Uveitis / Q000235:genetics / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta