Analysis of T-cell receptor Vbeta repertoire in liver-infiltrating lymphocytes in chronic hepatitis C.

BACKGROUND/AIMS: To examine the T-cell repertoire which is involved in the immunopathogenesis of chronic hepatitis, we analyzed the T-cell receptor Vbeta gene usage in liver-infiltrating lymphocytes by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical technique.

METHODS

Complementary DNA was synthesized from RNA which was extracted from 26 liver biopsy specimens and from peripheral blood lymphocytes from eight subjects, and amplified by RT-PCR. Radioactivity of each amplified product using 32P-labeled primers was measured and the percentage of each Vbeta expression was calculated.

RESULTS

The mean frequency of Vbeta5.1 (11.1%) in liver-infiltrating lymphocytes of chronic hepatitis C was highest among those of all Vbeta regions, and was significantly higher than that in both peripheral blood lymphocytes of chronic hepatitis C and liver-infiltrating lymphocytes of chronic hepatitis B. In the immunohistochemical analysis, Vbeta5.1-positive cells were mostly observed in portal areas where inflammatory reactions occurred. The sequences of the complementarity determining region (CDR)3 on T-cell receptor expressing Vbeta5.1 were examined in six patients with chronic hepatitis C. The sequences were similar to each other and all had one common amino acid (valine) irrespective of different HLA haplotype.

CONCLUSIONS

These data suggest that Vbeta5.1-positive cells are preferentially accumulated in the liver of chronic hepatitis C and are involved in the immunopathogenesis of the disease. Sequence analysis showed that Vbeta5.1-positive cells recognize a common conventional antigen and valine recognized at the same position of the CDR3 may be a key residue in determining an antigen/major histocompatibility complex contact point.