antigen presentation and enhancing antibody

Ian A. York iayork at
Wed Nov 1 12:22:41 EST 1995

In article <seq6-3110951301320001 at>,
Hoan Phan <seq6 at> wrote:
>I have a couple questions that been nagging at me, does anyone have any
>idea how is antigen presentation with MHCI in infected cells and cancer
>cells differred from those of presentation of antigen with MHCII in
>granulocytes, macrophages, dendrocytes, etc.. after ingestion and
>digestion of foreign invaders? What is responsible for the binding of
>those foreign antigen to the MHC complexes?

This question is too broad to answer properly here.  It's fundamental 
immunology; any immunology textbook will give you an answer.  It's 
reasonably well-understood.

>A second question - has there been any research done on distinguishing
>what make an antibody protective and how do some antibody become enhancing

These are two questions that are only partially related.  The first 
uestion is, Why are some antibodies neutralizing and some 
non-neutralizing?  The second is, why do some viruses showed 
antibody-mediated enhancement of infection?  The first is relevant to all 
viruses, the second only applies to a very limited subset of viruses.

Neutralizing vs. non-neutralizing antibody depends heavily on the precise 
epitope to which the antibody is directed.  In some cases the antibody 
binding to the particular region of the particular antigen may inhibit 
viral binding to ligands, or may block a conformational change required 
for viral entry, or something like that.  An interesting paper on some of 
the possible effects is 
 Wohlfart C.
Neutralization of adenoviruses: kinetics, stoichiometry, and mechanisms.
Journal of Virology.  62(7):2321-8, 1988

-and a review is in -

 Van Regenmortel MH.
 The conformational specificity of viral epitopes.
FEMS Microbiology Letters.  79(1-3):483-7, 1992

As far as antibody-mediated enhancement of infection, it's only seen in a
relative handful of viruses, of HIV may (or may not, in vivo) be one.  The
classic example is dengue virus.  The two basic requirements (fairly
obvious, really) are that the antibodies be non-neutralizing and the virus
be able to survive in an Fc-bearing cell.  Here are a couple of papers you
might find useful -

 Kurane I.  Rothman AL.  Livingston PG.  Green S.  Gagnon SJ.  Janus J. 
Innis BL.  Nimmannitya S.  Nisalak A.  Ennis FA. 
 Immunopathologic mechanisms of dengue hemorrhagic fever and dengue shock
 Archives of Virology - Supplementum.  9:59-64, 1994.

 Jiang SB.  Lin K.  Neurath AR.
 Enhancement of human immunodeficiency virus type 1 infection by 
antisera to peptides from the envelope glycoproteins gp120/gp41
Journal of Experimental Medicine.  174(6):1557-63, 1991

If you have more specific questions, send me a note.  
Ian York  (iayork at
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921     Fax  (617)-632-2627

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