We have recently addressed two questions related to the biological role of autoreactive CD4+ T cells in MS: (1) do the specificity and function of high avidity myelin-specific T cells in MS differ from controls, and is there a correlation between specificity and clinical phenotype? (2) Can we identify the specificity of CSF-infiltrating T cells in an unbiased way using combinatorial peptide chemistry as well as expression libraries employing cDNAs derived from MS brain tissue?