RESULTS OF A PHASE-I CLINICAL-TRIAL OF A T-CELL RECEPTOR PEPTIDE VACCINE IN PATIENTS WITH MULTIPLE-SCLEROSIS .1. ANALYSIS OF T-CELL RECEPTOR UTILIZATION IN CSF CELL-POPULATIONS

To identify a panel of multiple sclerosis patients (MS) for a phase I clinical trial of a T-cell receptor (TCR) peptide vaccine we character ized the T-cell populations present in the cerebrospinal fluids (CSF) of a large group of patients with respect to surface phenotype and sta te of activation, TCR beta chain utilization, features of the CDR3 jun ctional region, the extent of clonality and persistence of selected cl onotypes over time. These CSF cell populations consist of approximatel y 60% CD4+ T-cells, half of which bear IL-2 receptors, indicating thes e activated T-cells may be part of the pathogenic process in MS. When these activated CD4+ T-cells were selectively expanded in IL-2/IL-4 su pplemented cultures, an over-representation of several TCRV beta famil ies was noted in 39/47 patients, the most frequent being V beta 6.5, V beta 6.7, V beta 2, V beta 5 and V beta 4. Biased expression of vario us members of the V beta 6 family was seen in 21 of this group of 39 p atients. Clonal analysis of TCR beta 6 CDR3 sequences, revealed two no table features: clonal dominance and clonal persistence. CSF cells fro m two-thirds of MS patients contained a dominant clone comprising 50% or more of sequences and the same patient-specific clone could be show n to persist for up to 18 months. This clonal prevalence and over repr esentation of V beta 6 + TCR raises the possibility that immunization with a V beta 6 peptide vaccine may produce a regulatory immune respon se leading to a clinical benefit.