TAP independent pathways?

Ian A. York iayork at panix.com
Wed Aug 20 11:57:19 EST 1997

In article <1997Aug18.230441 at wehi>,
Vladimir Brusic, The Walter&Eliza Hall Institute <vladimir at wehi.edu.au> wrote:
>TAP-independent pathways of antigen processing have been often mentioned in 
>the literature, but without much explanation. The closest I could find was 
>that there are four other proteins that can transport peptides to the ER.

There are many examples of TAP-independent antigen processing, but so far
there's no global explanation; there seem to be multiple possible
pathways.  I'm not sure what you are referring to for the "four other
proteins"--can you give the reference for that?  

In general, it looks as if MHC I can bind to any peptide (with the
appropriate binding motif, of course) that reaches the ER; it doesn't
matter how the peptide gets there.  Most of the peptide reaches the ER via
TAP, but if you can get it in other ways, it might bind. 

One of the few cases in which the mechanism is known is the signal
sequence peptide binding to HLA-A2.  The binding motif of A2 fortuitously
matches the sequence in the signal sequence, so that when the signal
sequence peptidase clips it off it's available to bind.  The paper is J
Exp Med 180:1989-1994 (1994). 

Other than that, I think it's mostly phenomenology--the mechanisms are
unknown.  Examples of TAP-independent presentation include HIV env (Nature
364:158 (1993); J Immunol 154:6140-6156 (1995)). EBV LMP (J Virol
70:5357-5362 (1996)), and some Sendai virus protein(s) (several papers
from Jondal's lab, including Scand J Immunol 42:66-75 (1995)).   There's
nothing obvious in common, and there are enough differences in the various
descriptions that, I think, these are describing many different systems.

The only thing that's close to a review, as far as I know, is Siliciano
and Soloski (J Immunol 155:2-5 (1995)), which has about two paragraphs on
the phenomenon. 

      Ian York   (iayork at panix.com)  <http://www.panix.com/~iayork/>
      "-but as he was a York, I am rather inclined to suppose him a
       very respectable Man." -Jane Austen, The History of England

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