In article <35lvb5$gfh at jhunix1.hcf.jhu.edu>, ejf at welchlink.welch.jhu.edu
(Ephraim Fuchs) writes in response to my question regarding x-priming:
>1) As small tumors grow, they tend not to shed tumor-specific antigens.
If they do, they do so in small amounts, and the cells that are best
suited to picking up low concentrations of antigen are antigen-specific B
cells, which are also tolerogenic APCs for naive T cells. By the time a
tumor has outgrown its blood supply, it has already tolerized all tumor
antigen-specific T cells and so there is no cross-priming.
It is very difficult to know what might actually happen since we do not
have a mechanistic explanation for x-priming. Since most of the examples
in the literature involve cell-associated ag or even cellular debris
rather than soluble ag per se, I am inclined to believe that this ag is
captured by phagocytic cells. It is quite possible that necrotic or
apoptosing tumour cells might serve as a source of ag for x-priming rather
than shed soluble ag.
I also disagree with "the cells that are best
suited to picking up low concentrations of antigen are antigen-specific B
cells". Read "Sallusto, F., and A. Lanzavecchia. 1994. Efficient
presentation of soluble antigen by cultured human dendritic cells is
maintained by granulocyte/macrophage colony-stimulating factor plus
interleukin 4 and downregulated by tumor necrosis factor alpha. J. Exp.
Med. 179:1109". This paper clearly shows that DC can acquire soluble ag
with an efficiency similar to that of some ag-specific B cells.
Furthermore, DC in their immature stage are phagocytic and acquire
phagocytisable ags with 100X greater efficiency than soluble (my own
observations). Coupled with the fact that immature DC seem to be present
in virtually all tissues I think it is very likely that tumour ag, shed or
particulate, would be picked up by these cells and transported to lymphoid
tissues where it could prime a response.
KTano,
aka. Caetano Reis e Sousa, D.Phil.
LBS/LI/NIAID/NIH
Bldg. 10, Rm. 11N311
Bethesda, MD 20892
email: KTano at aol.com/caetano at pop.nih.gov
