THE CLONAL COMPOSITION OF MYELIN BASIC PROTEIN-REACTIVE ENCEPHALITOGENIC T-CELL POPULATIONS IS INFLUENCED BOTH BY THE STRUCTURE OF RELEVANTANTIGENS AND THE NATURE OF ANTIGEN-PRESENTING CELLS

Studies of experimental autoimmune encephalomyelitis (EAE) in rodents have revealed that encephalitogenic T cell lines reactive with myelin basic protein (BP) are frequently dominated by clones expressing a res tricted T cell receptor repertoire. Using the rat EAE model, we have b egun to examine the basis for clonal dominance within BP-reactive T ce ll lines. We find that variations introduced into the standard protoco l of periodic antigen stimulation produce marked shifts in the represe ntation of different clones within encephalitogenic T cell populations . For example, altering the source of antigen-presenting cells (APC),w hile holding antigen (BP) constant, and substituting BP from guinea pi g (GPBP) for that of the rat antigen (RBP) with constant APC, both cau se shifts in the composition of the dominant clones within BP-reactive T cell lines. Our results suggest that: (i) adherence to an invariant protocol of antigen challenge may lead to an underestimation of the d iversity of BP-reactive encephalitogenic T cell populations; and (ii) the minor structural differences between GPBP and REP not only cause t he weak immunogenicity of REP but also result in the alteration of dif ferent T cell subsets. These observations indicate that apparent restr ictions upon the repertoire of autoimmune T cells should be interprete d with caution when such cells are elicited by immunization with forei gn antigens.