ANALYSIS OF TCR BETA-CHAINS IN LEWIS RATS WITH EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - II - V-BETA-8.2(-CELLS WITH LIMITED CDR3 N REGION ADDITIONS DERIVE FROM HE ADULT THYMUS() T)

immunization of Lewis (LEW) rats with guinea pig myelin basic protein (MBP) induces a population of encephalitogenic CD4 T cells having spec ificity for the dominant immunogenic peptide of MBP, 68-86. The TCR be ta chains of these disease-causing T cells show three distinct feature s: they are almost exclusively V beta 8.2, they use AspSer as the firs t two amino acid residues of the third complementarity-determining reg ion (CDR3) and these junctional region sequences show few if any non-g ermline N-region nucleotide additions. This last feature raises the po ssibility that these autoimmune T cell precursors derive from TCR gene rearrangements occurring during early, perinatal ontogeny, a period w hen the enzyme terminal deoxynucleotidyl transferase (TdT), responsibl e for N region additions, is not expressed. An alternative possibility is that these features of the TCR of MBP 68-86-reactive T cells are d ictated by considerations of antigen selection throughout ontogeny bot h in the thymus and in the periphery - i.e. that such beta chains are conformationally the most appropriate for triggering by an epitope of 68-86 complexed to class II RT1.B-1 MHC molecules. We show here that a ctive experimental allergic encephalomyelitis, while delayed in onset, occurs in heavily irradiated animals, but not in the absence of a thy mus, a finding indicating that this autoimmune disease is caused by a T cell subpopulation derived from the post-irradiation adult thymus. T hese disease-causing T cells are heavily V beta 8.2(+), CDR3 AspSer(+) and use few N region additions. We conclude that T cells with these T CR II chain features can be generated in the adult thymus and most lik ely reflect requirements imposed by antigen selection.