In article <30v3jv$bpi at dns1.NMSU.Edu>, smori at nmsu.edu (Shahram Mori) says:
Everybody knows that in order for the
>autoreactive T-cells to be removed they must first be recognized as
>autoreactive. How would one know early during development that a T cell is
>autoreactive? The only possible way is for it to be recognized so. This
>recognition must be via cell to cell contact. Be it Macrophages,
>dendritic cells or other T-cells, these cells must be able to pick up all
>antigens, self and non self. So I would argue that antigen doesn't have to
>be labelled "foreign" early when the T-cell repetoir is being decided.
Disagree. Somewhere along the line, an antigen has to be labelled as
foreign. Consider CD4 and CD8 T cells separately. CD8 cells react with
MHC-peptides of intracellular origin. Most self-peptides will not be
displayed as part of intracellular self/not-self discrimination, so
"clonal ignorance" will predominate. A subset of intracellular self-
antigen-derived peptides will be displayed as a result of s/ns ic
discrimination, and deletion of the appropriate CD8 T cells will result.
CD4 cells react to MHC-peptide presented by cells which have obtained
the protein externally. The s/ns discrimination process is here removed
from the CD4 cell and occurs at the level of B cell education. A nascent
B cell goes through the self/not self discrimination process. If its
receptors do not react with self antigenic determinants (presentation by
another cell not critical), then it survives and goes on to secrete
natural antibody. This natural antibody only reacts with "foreign"
antigen, with the result that only foreign antigens end up being
presented to CD4 cells.
>From Transgenic mice studies we know that if for example MHC D2 molecule is
>introduced into MHC H-2b there is no T-cell response observed against
>the D2,while if the D2 gene is modified in such a way that lacks the portion
>for transmembrane localizatiion
>resulting in the molecule being secreted into the blood, there is no B or T
>cell tolerance induced.This provides evidence that there can be no
>tolearnce induced if the antigen is circulating without being picked up and
>that the antigens must be picked up randomly in order to be recognized.
I suggest to give a good reference on this and suggest to Matt Buchanan
that we discuss it in a future Bionet.immunology monthly journal club.
Sincerely, Don Forsdyke
Discussion Leader. Bionet.immunology
