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T cells are known for their ability to bind multiple antigens, owing to the degeneracy of the recognition sites on their receptors. [I] When examining the structure of the T cell receptor, we can observe the ɑ and β chains which have a highly variable region, in their extracellular domain:

enter image description here

From what I understand, TCR degeneracy means that one receptor can bind to different antigens.

In comparison, the B cell receptor consists of a recognition site that contains a membrane-bound isotope of immunoglobulin. Again, from what I gather, variation in both the Ig on B cells and the TCR occur as a result of genetic recombination. [II]

enter image description here

Question:

Does the membrane-bound Ig in the BCR exhibit the same degeneracy as TCRs? Does variation caused by V(D)J recombination work the same way for both these receptors?

References:

[I] https://en.wikipedia.org/wiki/T_cell_receptor

[II] https://en.wikipedia.org/wiki/V(D)J_recombination

[Images] http://what-when-how.com/acp-medicine/adaptive-immunity-antigens-antibodies-and-t-cell-and-b-cell-receptors-part-2/

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    $\begingroup$ What do you mean by "degeneracy". $\endgroup$ – Chris Sep 24 '15 at 7:18
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    $\begingroup$ "From what I understand, TCR degeneracy means that one receptor can bind to different antigens." $\endgroup$ – Hernandez Sep 24 '15 at 7:45
  • $\begingroup$ Quick answer: No, individual T cells can only bind one antigen with their TCRs, just like B cells. $\endgroup$ – MattDMo Sep 24 '15 at 19:47
  • $\begingroup$ From the wiki TCR article: "TCRs have very high degree of antigen specificity, despite of fact that the affinity to the peptide/MHC ligand is in the micromolar range." $\endgroup$ – MattDMo Sep 24 '15 at 20:00
  • $\begingroup$ From the same article: "The binding between TCR and antigen is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen and many antigens are recognized by the same TCR." $\endgroup$ – Hernandez Sep 25 '15 at 0:25
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This is incredibly oversimplified, but the short answer is that both T and B cells can have degenerate recognition, though the molecular mechanisms are somewhat different.

T cells recognize linear sequences of amino acids that have been excised from their parent proteins, from 8 to 16 or so amino acids long, and that are associated with MHC proteins. The association with MHC proteins depends on the specific sequence of amino acids, and you can think of this association as depending on a number of amino acids (let's say 4 or 5) that point "down" into the MHC. That leaves maybe 4-10 amino acids pointing "up" that can interact with the T cell receptor. If you search for a random set of 4 amino acids with a given spacing, it's quite likely that it will turn up several times in a large protein database; even more often if you allow some degeneracy (similar amino acids can substitute sometimes). Therefore, yes, T cells tend to have a moderate amount of degeneracy in their epitope recognition. However, while search a whole database may find duplicates, the degeneracy is not terrible, and the MHC binding requirement also reduces it quite a bit. Also, of course, during T cell development, TcRs that have broad and degenerate recognition of many structures are selected against. So T cells are definitely cross-reactive, and sometimes extensively so, but in single individuals it's probably not a common thing. (Ray Welsh and Liisa Selin have looked at cross-recognition between viruses and find quite a bit of cross-reactivity, though, so this may be understated.)

Antibodies, unlike T cells, recognize conformational epitopes rather than linear sequences. However, just as with linear epitopes, it's not impossible for two unrelated proteins to end up with similar conformations, even with rather different amino acids. As well, antibodies can be more or less "forgiving" in their recognition; some are extremely specific, but others can interact with a wider range of shapes. You can imagine a "flat" antibody binding surface that is rather generic, that could interact with many different shapes. Again, B cells with broad cross-recognition are selected against during development, though not as rigorously as are T cells.

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  • $\begingroup$ There's a lot more data on TCR degeneracy than for the BCR, but they do have a quantitative study here on CD8+ T cell cross-reactivity and they found that a single TCR was capable of responding to over 10^6 decamer peptides. $\endgroup$ – CKM Dec 9 '15 at 22:01
  • $\begingroup$ Yeah, but that's not every TcR -- that's one specific one that, because it's autoimmune, must have avoided much of the usual developmental checks already. Probably most TcR that have gone through the negative selection process would have less degeneracy than that one. But there's certainly still room for recognition of a large number of peptide variants. $\endgroup$ – iayork Dec 9 '15 at 22:13
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First of all, you have to distinguish between the term antigen and epitope. An epitope is a specific amino acid sequence that is recognized by the TCR/BCR. The epitope does not have to be a linear amino acid sequence, a BCR can also be recognize conformational epitope. An antigen is composed of multiple epitopes. Since there are many conserved structures among the proteins, it more than convincing that one TCR can bind more than one antigen as long as the antigens contain the epitope (https://en.wikipedia.org/wiki/Antigen).

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Some of the information contained in this post requires additional references. Please edit to add citations to reliable sources that support the assertions made here. Unsourced material may be disputed or deleted.

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    $\begingroup$ Please add references to your answer. $\endgroup$ – Dexter Dec 9 '15 at 11:53
  • $\begingroup$ A T cell epitope DOES have to be a linear epitope. $\endgroup$ – iayork Dec 9 '15 at 13:40

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