Background

Several groups have Observl'CI two distinct yet related phenomena occurring at the level of the individual patient or rodent strain: restricted V-gene usage and oligoclonalexpansion. Workshop participants generally agrt.'t.'CI that TCR V-gene usage is restrictl'd to Iimitl'CI Va. and/or Vf3 combinations in MBP-reactive clones from given human individuals or rodent strains. However, V-gene usage may vary widely between individuals and strains. In humans, this conclusion has bct'n supported by studies both on MBP-reactiVl'

T-cell clones derived from peripheral bloocF-" and on clones of undetermined specifiCity isolated from CNS tissue9, 1O. Two groups found greater V-gene restriction in MS patients than in healthy subjects5, 6, suggesting that V-gene restriction may be related to some aspect of the disease process. Similar results were obtained in individuals with. l variety of other autoimmune diseases [including rheumatoid arthritis (RA)] 11-20. Restricted V-gene usage in MBP recognition has also been observed within particular rodent strains. Lewis rat clones reactive against MBP 6R-88 use V (38 almost excIu-sively~ I-2', By contrast, rat clones specific for MBP R5-99 or 87-99 are not restricted to V (38, suggesting a direct correlation between peptide specificity and V-gene usage26, 27. In several strains of H-2" mice, MBP-specific T-cell clones also frequently use V [38, despite the fact that they recognize a different major histocompatibility complex (MHO class II molecule and a different MBP fragment (MBP 1-11) than do Lewis rat V [38+ clones~ X-ll. In SILlJ (H-2') mice, which lack the V (38 gene segment, V (317a is preferentially used in recognition of MBP 89-101 (Refs: U,: Bl. Rodents with other experimental autoimmune diseases also exhibit varying degrees of V-gene restriction within given strains 1-14".