Clonal diversity of basic protein specific T cells in Lewis rats recovered from experimental autoimmune...

T cell lines selected from Lewis rats recovered from experimental autoimmune encephalomyelitis (EAE) respond not only to the immunodominant 72-89 epitope of basic protein (BP), but also to secondary epitopes including the I-A restricted 43-67 region of guinea pig (Gp) BP and the I-E restricted 87-99 sequence of rat (Rt) BP. The current study demonstrates at the clonal level the diversity of T cell responses to Gp- and Rt-BP in EAE-recovered rats. As predicted from the response pattern of BP-selected T cell lines, T cell clones from the lines responded to both the dominant and secondary epitopes of BP. In addition, a new majority clonal type was identified that responded to whole BP but not to epitopes represented on enzymatic cleavage fragments or synthetic peptides spanning the BP molecule. Clones representative of each of the three types of Gp-BP responses were characterized for phenotype, major histocompatibility complex restriction, and biologic activity in vivo. All of the clones were strongly CD4+ and co-expressed CD8 at modest levels as measured by both immunofluorescence and Northern blots. All three T cell specificities were I-A restricted. However, only the 72-89 responsive clone could transfer clinical EAE, due most likely to its unique ability to respond to Rt-BP. In contrast, the Gp-BP 43-67 reactive T cell clone transferred protection against EAE, whereas the whole Gp-BP reactive clone transferred delayed-type hypersensitivity response but was neither encephalitogenic nor protective. Thus, the recovery process from EAE is distinguished by an increased diversity of protective clones as well as innocuous clones that may be spawned as encephalitogenic T cells are regulated.