Cross-reactivity of T-cell clones specific for altered peptide ligands of myelin basic protein

We have determined that certain altered peptide Ligands (APLs) can induce T -cells specific for the native peptide myelin basic protein (MBP) p85-99 to secrete Th2-type cytokines such as IL-4 and IL-5 in the absence of signifi cant Th1-type cytokines. However, it is not known whether stimulation with APLs will activate autoreactive T cells or a distinct population of cells. In the present study, 18 T-cell clones that reacted with either MBP p85-99 or one of three APLs of the peptide substituted at TCR contact residues wer e generated. T-cells were tested functionally for their reactivity to the o riginal stimulating peptide as well as to the MBP APLs, In addition, the T- cell receptor (TCR) alpha and beta chains of each of these clones were sequ enced. In a series of T-cell clones isolated hom a multiple sclerosis patie nt, stimulation of T-cells with the APL 93A, which has an alanine for lysin e substitution at the TCR contact residue 93, did not induce substantial pr oliferation of MBPp85-99-specific T-cell clones, indicating that a distinct set of T-cell clones was induced. However, this was not the case for anoth er set of T-cell clones from a different individual in which the 93A peptid e induced clonal expansion of T-cells highly reactive with the native MBPp8 5-99 antigen. Thus, the potential beneficial effect of using APLs to induce downregulatory cytokines appears to depend on the specific T-cell repertoi re of the individual patient. (C) 1999 Academic Press.