Predominant usage of V beta 8.3 T cell receptor in a T cell line that induces experimental autoimmune uveoretinitis (EAU).
Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease induced in animals by immunization with retinal proteins (or synthetic fragments derived from them) in adjuvant, and it is considered a model of human autoimmune diseases of the eye. To study the T cell clonotypes that may be involved in EAU, we analyzed the T cell repertoire of three related T cell lines: the pathogenic line LR16, specific to the major uveitogenic epitope of IRBP; its pathogenic subline J; and its nonpathogenic subline A. We examined the expression of the genes coding for the variable regions of the 20 known Lewis rat T cell antigen receptor (TCR) V beta families. The nonpathogenic subline was found to contain mostly T cells expressing V beta 5, V beta 8.2, and V beta 19 while the pathogenic subline consisted mainly of cells expressing V beta 8.3 TCRs. Genomic Southern blot analysis of DNA from the pathogenic subline showed that V beta 8.3-expressing T cells were the dominant clonotype, and DNA sequence analyses of V beta 8.3 cDNAs revealed that two V beta 8.3 TCRs were expressed in the pathogenic subline. One of the V beta 8.3 cDNAs encoded a variable region gene segment identical to previously reported rat V beta 8.3 TCR while the other differed by two amino acids in the second complementarity determining region (CDR2). Taken together with previous data showing overrepresentation of V beta 8-expression in T cell lines that induce EAU, but not in nonuveitogenic T cell lines, our results suggest that V beta 8.3-expressing T cells represent a pathogenic clonotype in IRBP-induced EAU.
Egwuagu
C E
CE
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
Bahmanyar
S
S
Mahdi
R M
RM
Nussenblatt
R B
RB
Gery
I
I
Caspi
R R
RR
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D004247:DNA / Q000032:analysis; D005123:Eye / Q000473:pathology; D005136:Eye Proteins; D015870:Gene Expression; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics*; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D004247:DNA; D005136:Eye Proteins; D012313:RNA; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial