seq6 at sfsuvax1.sfsu.edu (Hoan Phan) wrote:
>Hello netters,
>>I have a couple questions that been nagging at me, would 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?
First of all I do not know what your background is in immunology.
However, I would like to mention here that foreign antigens bind to MHC
in the form of small ligands i.e., peptides of 8-10 amino acids in the
case of MHC class I and about 12-25 (on an average) in the case of class
II molecules. The presence of these peptides in the binding groove of
MHC molecules is a necessity for the stability of the trimeric MHC
complex. It is therefore imminent that uninfected of normal cells will
have MHC molecules with peptides derived from self proteins. There are
recent evidences showing that each MHC allelomorph, especially class I,
has a particular characteristic at certain amino acid positions of the
peptide. One or more of these seem to be absolutely essential for
binding to that particular molecule. These are called 'anchor residues'
and the combination of such residues is called the 'allele-specific
peptide motif.' The motifs are mostly responsible for binding to MHC
molecules and this happens irrespective of whether the peptide is derived
from self of foreign protein.
Now as to the question of the difference between infected cells and tumor
cells with class I and other cells with class II presentation, first of
all class I molecules are present on most nucleated cells although at
varied amounts. Moreover, class I molecules will only elicit cytotoxic T
lymphocyte response (i.e., specific cell mediated immune response). On
the other hand class II molecules are present only on so called
professional antigen presenting cells (B cells, Macrophages, Dendritic
cells, Langerhans cells; they can also be induced on certain other cell
types like endothelial cells) and these molecules elicit T helper type
response leading to humoral immunity (i.e., antibody production). The
pathways of presentation differ radically between the two systems.
>>A second question - has there been any research done on distinguishing
>what make an antibody protective and how do some antibody become enhancing
>antibody - apparently they both bind to the viral particle - What makes
>one neutralizing and the other enhancing the introduction of the virus
>into the host thru (I guess) its Fc receptor? This question is relevant to
>HIV infection. Thanks much in advance, and any reference would be greatly
>appreciated.
Antibodies may bind to the viral particle but the epitope they bind may
not be involved in any of the steps involved in viral entry into the host
cell. This will lead to the protein involved in viral entry still being
open and the virus will still be able to infect. Only those antibodies
which bind to proteins which are actually involved in attachment and
penetration of the viral particle will "neutralize" the infectivity of
the viral infectivity (some times this could also be due to a steric
hindrance). Therefore non-neutralizing antibodies will not protect.
In the case of antibody-mediated enhancement of viral entry (as it
happens with Dengue virus), there could be two possible mechanisms. One
is that the virus actually infects cells bearing Fc receptors and takes
up the virus as a complex with the antibody (a related example is
Epstein Barr virus which utilizes a complement receptor for its entry).
The other possible mechanism is that the cell bears Fc receptors, but the
virus binds its receptor when the antibody brings the virus closer to the
actuall viral receptor.
I may not have answered all your questions and might also have introduced
more questions. However, I hope this helps in some way at least.
Nagendra R. Hegde
Graduate student
Univ. of Nebraska-Lincoln
nhegde at crcvms.unl.edu
