werner@aecom.UUCP (Craig Werner) (12/16/86)
!
[Abstract of the Week, AOTW, is a weekly (more or less) feature of sci.bio]
! The Nucleocapsid of Hepatitis B Virus is Both a T-Cell-Independent
! and a T-Cell-Dependent Antigen.
! Milich DR and McLachlan A
! Science 234:1398 (12 Dec 1986)
One characteristic of the immune response during hepatitis B virus
(HBV) infection in humans is the vigorous production of antibodies of
immunogloulins (Ig) M and G to nucleocapsid antigen (HBcAg). In this
study HBcAg was shown to be similarly immunogenic in mice. When injected
into athymic (nude) B10.BR and athymic BALB/c mice, HBcAg induced IgM and
IgG class antibodies in spite of the absence of T cells in nude mice. In
euthymic mice, HBcAg efficiently stimulated T-cell proliferation in vitro
and helper T-cell function in-vivo. The dual functions of HBcAg as a
T-cell independent and a T-cell dependent antigen may explain its
enhanced immunogenicity. Denaturation of HBcAg yields a nonparticulate
antigen designated HBeAg; when HBeAg was used as the immunogen, antibody
production required helper T-cell function. Although HBcAg and HBeAg are
serologically distinct, they are structurally related, and in these
experiments were highly cross-reactive at the T-cell level. These
results suggest that the elevated levels of IgM antibodies to HBc and the
enhanced immunogenicity of HBcAg during HBV infection in humans reflrect
the ability of HBcAg to directly activate B cells to produce antibodies
to HBc in the presence or absence of HBcAg- or HBeAg-sensitized T-cells.
Note: if you are like me, you are probably wondering what an
intracellular antigen like HB core antigen is doing being recognized by
the immune system in the first place. Well, the phenomenon is not an
isolated one, although the lack of a need for Helper T-cells is. Even so,
it has always really bothered me. After all, the immune system should
only be seeing things that are exposed, or should it? Explanations are
beyond me...
--
Craig Werner (MD/PhD '91)
!philabs!aecom!werner
(1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517)
"It's hard to argue with someone who knows what he's talking about."oliver@unc.UUCP (Bill Oliver) (12/18/86)
In article <740@aecom.UUCP> werner@aecom.UUCP (Craig Werner) writes: >! > >Note: if you are like me, you are probably wondering what an >intracellular antigen like HB core antigen is doing being recognized by >the immune system in the first place. Well, the phenomenon is not an >isolated one, although the lack of a need for Helper T-cells is. Even so, >it has always really bothered me. After all, the immune system should >only be seeing things that are exposed, or should it? Explanations are >beyond me... > >-- > Craig Werner (MD/PhD '91) I'm not really sure, but two possible explanations come to mind. The first is that, like almost all viruses, complete packaging of the virion is not 100% efficient. When the host cell dies, it releases both the complete, infectious, virions as well as the incomplete parts. In HBV, of course, the envelope is produced (if my memory serves me right -- I don't have my references handy) in excess as spherules, which can be detected in the circulation in active disease. This excess of envelope would argue for high efficiency of covering up the core.... Leading to the second possiblity -- that the circulating complete virion has the envelope removed by a circulating factor. In the lab, you need some sort of detergent to rip off the envelope, but there is no reason that it con't be done somewhere by the body. I'd be willing to bet that incomplete packaging leads to dumping of the core, and that a circulating factor, probably immune mediated, breaks up the core, releasing the e antigen. While no c is ususally found in the bloodstream, e antigen is found in acute illness and is an integral part of the core -- suggesting that perhaps the core was released and then degraded. This would allow exposure of both c and e antigens to the immune system even though only the e is found in circulating blood. Sound good? Bill "People's Pathologist"