We have investigated the clonality of -chain T-cell receptor (TCR) transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year old child who developed a multiphasic disseminated encephalomyelitis following an infection with hepatitis A virus. We amplified -chain TCR transcripts by nonpalindromic adaptor (NPA)-PCR-V-specific PCR. TCR transcripts from only five V families (V13, V3, V17, V8, and V20) were detected in CSF. The amplified products were combined, cloned, and sequenced. Sequence analysis revealed in the CSF substantial proportions of identical -chain of TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of 35 (48%) transcripts were 100% identical, demonstrating a major V13.3 D2.1 J1.3 clonal expansion. Six of 35 (17%) transcripts were also 100% identical, revealing a second V13 clonal expansion (V13.1 D2.1 J1.2). Clonal expansions were also found within the V3 family (transcript V3.1 D2.1 J1.5 accounted for 5 of 35 transcripts [14%]) and within the V20 family (transcript V20.1 D1.1 J2.4 accounted for 3 of 35 transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal expansions in the CSF of this patient following infection with hepatitis A virus. Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell clones exhibited substantial homology to myelin basic protein-reactive T-cell clones. In contrast, all V TCR families were expressed in peripheral blood lymphocytes. Oligoclonal expansions of T cells were not detected in the peripheral blood of this patient. It remains to be determined whether these clonally expanded T cells are specific for hepatitis A viral antigen(s) or host central nervous system antigen(s) and whether molecular mimicry between hepatitis A viral protein and a host protein is responsible for demyelinating disease in this patient.