A vigorous virus-specific CD4+ T cell response may contribute to the association of HLA-DR13 with viral clearance in hepatitis B.
A strong virus-specific CD4+ and CD8+ T lymphocyte response to hepatitis B virus (HBV) has been associated with viral clearance, but little is known about factors determining the individual's ability to mount such a T cell response. Recently a strong association between the HLA class II allele DR13 and a self-limited course of HBV infection has been described. In the present study of 33 patients with acute hepatitis 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; 10,552 ct/min)) than patients without HLA-DR 13 (1365 ct/min (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 both patient groups. Moreover, among 14 HBV core-specific CD4+ T cell clones from two patients with HLA-DR13, only one T cell clone was HLA-DR13-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 may either be due to more proficient antigen presentation by the HLA-DR13 molecules themselves or a linked polymorphism in a neighbouring immunoregulatory gene.
Diepolder
H M
HM
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
Jung
M C
MC
Keller
E
E
Schraut
W
W
Gerlach
J T
JT
Grüner
N
N
Zachoval
R
R
Hoffmann
R M
RM
Schirren
C A
CA
Scholz
S
S
Pape
G R
GR
D000208:Acute Disease; D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D000939:Epitopes; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007565:Jaundice / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation
D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C097337:HLA-DR13 antigen; D006512:Hepatitis B Core Antigens