STRUCTURE AND SPECIFICITY OF T-CELL RECEPTORS EXPRESSED BY POTENTIALLY PATHOGENIC ANTI-DNA AUTOANTIBODY-INDUCING T-CELLS IN HUMAN LUPUS

\The production of potentially pathogenic anti-DNA autoantibodies in S LE is driven by special, autoimmune T helper (Th) cells. Herein, we se quenced the T cell receptor (TCR) alpha and beta chain genes expressed by 42 autoimmune Th lines from lupus patients that were mostly CD4+ a nd represented the strongest inducers of such autoantibodies. These au toimmune TCRs displayed a recurrent motif of highly charged residues i n their CDR3 loops that were contributed by N-nucleotide additions and also positioned there by the recombination process. Furthermore, Th l ines from four of the five patients showed a marked increase in the us age of the V alpha 8 gene family. Several independent Th lines express ed identical TCR alpha and/or beta chain sequences indicating again an tigenic selection. 10 of these Th lines could be tested further for an tigenic specificity. 4 of the 10 pathogenic anti-DNA autoantibody-indu cing Th lines responded to the nonhistone chromosomal protein HMG and two responded to nucleosomal histone proteins; all presented by HLA-DR molecules. Another Th line responded to purified DNA more than nucleo somes. Thus, these autoimmune Th cells of lupus patients respond to ch arged epitopes in various DNA-binding nucleoproteins that are probably processed and presented by the anti-DNA B cells they selectively help .