What is an MHC restricted peptide?

I got this definition from wikipaedia, but cannot exactly extract what the phrase MHC restricted peptide means.

MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a given T cell will recognize a peptide antigen only when it is bound to a host body's own MHC molecule. Normally, as T cells are stimulated only in the presence of self-MHC molecules, antigen is recognized only as peptides bound to self-MHC molecules.

I have not studied biology since last 8 years and now I am going through it because I need it for my research. So if someone can describe it in simple language it would be very helpful.


First of all MHC stands for major histocompatibility complex. There are two types of MHC.

MHC type one is present on all of our cells with a nucleus. The purpose of these protein complexes is called antigen presentation. T-cells cannot recognize free antigens on their own, it has to be presented to them in the proper way. This is what these proteins do. In every cell there are lots and lots of proteins, that get digested to small polypeptides (short aminoacid sequences) by proteases during the natural recycling process. The cell takes a small portion of these polypeptides and presents them on its surface through MHC I complexes, that the immune system can read. This is like the cell saying to the immune syytem that "hey I got these proteins in me". Now if the cell is infected (by a virus most likely) then the "attacker's" proteins get digested and presented as well and its like saying " hey I'm infected and the attacker has these proteins".

MHC II serves similar function but it is only present on professional antigen presenting cells (APCs). These complexes present peptides derived from proteins consumed and digested through phagocytosis or receptor mediated endocytosis. It's like saying "hey we got a larger attacker and it has these proteins"

So, long story short T-cells cannot recognise antigens on their own it needs to be presented to them on MHC complexes and then and only then can they be activated.

Edit: A list of useful articles in the topic of antigen processing / presentation for further details:

January 14, 1998 14:59 Annual Reviews AR052-12 Annu. Rev. Immunol. 1998. 16:323–58 MECHANISMS OF MHC CLASS I–RESTRICTED ANTIGEN PROCESSING Eric Pamer and Peter Cresswell

Cell, Vol. 76, 287-299, January 28, 1994. MHC-Dependent Antigen Processing and Peptide Presentation: Providing Ligands for T Lymphocyte Activation

Terry Y Nakagawa, Alexaiider Y Kudensky The role of lysosomal proteinases in MHC class Il-mediated antigen processing and presentation
This one may require subscription.

and the wiki page :)

  • 2
    $\begingroup$ I would also like to add an analogy to poka.nandor's answer that I used to explain my girlfriend (who studies law lol) MHC restriction. Imagine you have a plate and a sandwich. When the sandwich is not on the plate you do not know that it is a sandwich. When someone puts the sandwich on the plate you suddenly realise it is a sandwich. Basicly T-cells require the context of the MHC to recognise peptides. $\endgroup$ – Wolgast Mar 30 '15 at 13:36

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