We know that the adaptive immune system recognizes foreign particles when their proteins are expessed of the the surface of T-cells, complexed with MHCs. But MHCs present only short peptides of length 8-11 amino acids long. How is it that every antigen has one characteristic 8-11 residues long stretch in some protein of its which none of the host's protein has. Conversely, how is it that this 8-11 amino acid long peptide, which the body is recognizing as foreign is not found in any protein of any cell of our body?


For starters, your conception of antigen presentation seems a bit off, but that's not the crux of your question. There's around 10^15 different sequence permutations for a peptide 11-mer. Despite that, it's actually likely that highly conserved regions of some proteins will be present in both the pathogen and the host. T cells will not recognize them, however, as they are negatively selected in the thymus.

  • $\begingroup$ This is not completely true. One part of the adaptive immune system actively recognizes and tolerates own oligopeptides. $\endgroup$ – inf3rno Apr 28 '15 at 19:08
  • $\begingroup$ @inf3rno Which component is that? $\endgroup$ – canadianer Apr 28 '15 at 19:12
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    $\begingroup$ en.wikipedia.org/wiki/Regulatory_T_cell "Regulatory T cells are involved in shutting down immune responses after they have successfully eliminated invading organisms, and also in preventing autoimmunity cells." - Ofc. most of the self-reactive T-cells are destroyed by negative selection, or probably (I guess) transformed into regulatory T-cells. I have to read more in the topic, but it's too complex, I have to write a program, which can maintain a knowledge graph. $\endgroup$ – inf3rno Apr 28 '15 at 19:20
  • $\begingroup$ Another part of the puzzle: en.wikipedia.org/wiki/Regulatory_B_cells $\endgroup$ – inf3rno Apr 28 '15 at 19:26
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    $\begingroup$ @inf3rno I don't think Tregs can be said to be actively recognizing self antigens. It seems that Treg recognition of self is an exception rather than the rule. $\endgroup$ – canadianer Apr 28 '15 at 23:05

The immune system is the most beautiful, complex biological process that operates on a scale that it can be termed as engineering.

MHC polymorphism:

MHC's have two particular properties that give it flexibility in the face of the antigen: Its polygenicitcy (it contains several different MHC class I and MHC class II genes with different ranges of peptide-binding specificities) and secondly, MHCs are polymorphic (having multiple variants of each gene within the population).

Note: MHCs are also called HLA (Human Leukocyte Antigen)

enter image description here

So as you can see, there is a lot of possible variation possible. I'd recommend reading through this:


From the source above:

The outstanding feature of the MHC molecules is their extensive polymorphism. This polymorphism is of critical importance in antigen recognition by T cells. A T cell recognizes antigen as a peptide bound by a particular allelic variant of an MHC molecule, and will not recognize the same peptide bound to other MHC molecules.

This behavior of T cells is called MHC restriction. Most MHC alleles differ from one another by multiple amino acid substitutions, and these differences are focused on the peptide-binding site and adjacent regions that make direct contact with the T-cell receptor.

At least three properties of MHC molecules are affected by MHC polymorphism: the range of peptides bound; the conformation of the bound peptide; and the direct interaction of the MHC molecule with the T-cell receptor. Thus the highly polymorphic nature of the MHC has functional consequences, and the evolutionary selection for this polymorphism suggests that it is critical to the role of the MHC molecules in the immune response.

  • $\begingroup$ While a good explanation, this does not address the question. $\endgroup$ – canadianer Apr 28 '15 at 18:16
  • $\begingroup$ @canadianer Apologies, misread the question. Editing the answer now. $\endgroup$ – Rover Eye Apr 28 '15 at 18:25

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