A VIGOROUS VIRUS-SPECIFIC CD4(-CELL RESPONSE MAY CONTRIBUTE TO THE ASSOCIATION OF HLA-DR13 WITH VIRAL CLEARANCE IN HEPATITIS-B() T)

A strong virus-specific CD4(+) and CD8(+) T lymphocyte response to hep atitis B virus (HBV) has been associated with viral clearance, but lit tle is known about factors determining the individual's ability to mou nt such a T cell response. Recently a strong association between the H LA class II allele DR13 and a self-limited course of HBV infection has been described. In the present study of 33 patients with acute hepati tis B we show that individuals carrying HLA-DR13 mount a more vigorous CD4(+) T cell response to HBV core (5706 ct/min (25th/75th percentile 3239 ct/min, 10552 ct/min)) than patients without HLA-DR13 (1365 ct/m in (490 ct/min; 5334 ct/min); P = 0.006). However, peptide epitopes aa 50-69, aa 61-85, and aa 81-105 were recognized most frequently by bot h patient groups. Moreover, among 14 HBV core-specific CD4(+) T cell c lones from two patients with HLA-DRIS, only one T cell clone was HLA-D R13-restricted. Our data suggest that the beneficial effect of the HLA -DR13 alleles on the outcome of HBV infection could be explained by a more vigorous HBV core-specific CD4(+) T cell response, which map eith er be due to more proficient antigen presentation by the HLA-DR13 mole cules themselves or a linked polymorphism in a neighbouring immunoregu latory gene.