MHC molecules are constantly translated which is evident even in the absence of efficient antigen presentation, for instance in TAP deficient cells. Having said that, IFNgamma and TNFalpha have been shown to further upregulate molecules associated with antigen processing and presentation including MHC

Hi,

your question is a little vague. It is difficult to answer you without writing pages. You should try to ask it again by rephrasing the question in terms of nature of the antigen presenting cell you're interested in, and the nature of the MHC you're trying to study (class I vs class II). Very briefly the class I and class II MHC molecules traffic very differently inside the cells that express them and encounter the antigen at different sites. Newly synthesized MHC I encounters the Ag in the ER (but not only) whereas the MHC II encounters the Ag in late endosomal vesicules (not only).

hope this helped, don't hesitate asking me directly if you need more info

Best

Georges

MHC molecules are constantly translated which is evident even in the absence of efficient antigen presentation, for instance in TAP deficient cells. Having said that, IFNgamma and TNFalpha have been shown to further upregulate molecules associated with antigen processing and presentation including MHC

Thanx for the answers,I was referring to both MHC class 1 and 2,having learnt just now that the antigens to be presented to each class are processed differently, and yet the gene is always turned-on,I wish to know whether the MHC (both) receptor site is antigen specific, just as in the insulin receptor is specific for insulin. I am trying to think that if it is, then how is antigen processing and fragmentation kept in check to ensure that an antigen is hydrolysed in such a way that it specifically fits into the MHC receptor sites, also i'd like to think that the polymorphisms work more like the hand and glove (induced-fit) model of enzyme activity, where by the receptor sites will adjust to accommodate the antigen

Proteosomal cleavage creates a c-terminal suitable for MHC (1, for instance) binding of the peptides. The peptides are also typically extended at their N-terminal to suit its binding to MHC molecules. So it is not a hand-glove thing, but more like a hand-holding-a gripped bat kinda thing. Further, IFNg has been shown to enhance the generation of peptides more suitable for MHC binding by better proteosomal cleavage. For more info check out DOI: 10.1146/annurev.cellbio.24.110707.175347

Hope this helps.

Yes,it does help. Thanx alot

This is a useful paper: http://www.nature.com/nri/journal/v11/n12/pdf/nri3084.pdf

True that MHC class I expression is always on, and ubiquitous on all nucleated cells.However only some cells express MHC II molecules (professional antigen presenting cells, mainly DCs, B cells and some monocytes/macrophages). Also, MHC II expression can be locally induced by IFNg in different cell types.

As Samarchith already explained, proteosomal processing of cytoplasmic proteins (mainly) are the major contributors of the peptides available to bind the MHC I molecules. The interaction between the peptides and the binding groove of each MHC molecule is subjected to affinity competition, so the MHC molecules can bind a large set of peptides with different affinities. To help out there are some resident molecules of the ER that play the role of chaperones (Tapasin, calreticulin and others) bending the rules of affinity a little and permitting the association of many different peptides to the MHC.

On the other hand the MHC II-peptide complex gets formed in the endosomes. Although the MHC II molecule is formed in the ER, its binding groove is protected from interacting with cytoplasmic and ER peptides by another protein called the invariant chain (Ii). Ii is then processed gradually in the endosomal pathway and exchanged with an antigenic peptide (usually coming from the extracellular milieu) with the help and the editing of a chaperone non-classical MHC II molecule (HLA-DM or H2-M). In this case also, the presence of the chaperone molecule affects the peptide pool presented by the MHC molecules in a way that is not only driven by affinity for the binding groove hence influencing immunogenicity.

^^ That is a very crisp explanation Georges.

(And by the way, we had your group's immunity paper on our Journal club last year. Very interesting, neat work to say the minimum- at least in comparison to a lot of things they publish at times. Kudos!!)

Thx Samarchith.

Cheers