The case for allele-specific recognition by the T cell receptor (TCR)

A recent published review article discusses how T cell receptor (TCR) variable regions (V) might have been naturally selected to recognize self-molecules (MHC) important for presenting foreign pieces of proteins (usually peptides derived from infectious agents like bacteria, viruses and parasites).

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Figure 1.The T cell receptor – MHC Class II with a peptide interaction is schematically shown. Photo: Zlatko Dembic, IOB/UIO.

T cell receptors interact with MHC molecules with the peptide in the groove between the two alpha helices of the molecule. MHC of the humans are called Human Leukocyte Antigens or HLA, which are important for tissue transplantation too. Thus, the name - MHC derives from such a function – major histocompatibility complex (of proteins). (Histo = tissue, compatibility= ability to tolerate foreign tissue, or organ from another person). The TCR-MHC interactions are conserved in the evolution, and each species of higher animals has their own sets of alleles and preserved interactivities.


In the review it has been suggested that TCR-MHC “interacting ability conservation” is due to interaction of three specific regions on the interacting surfaces- as depicted on the Figure 2. The region on the TCR molecule called #tope3 (Fig.2c) is the only one predicted theoretically to be “free” to interact with foreign peptides (usually bacterial, viral or parasitic). This is important because via such a mechanism the adaptive immune system can recognize pathogens and protect us from infections.

Figure 2. TCR V region sites in contact with peptide-MHC - a schematic view from the top. A. TCR-pMHC view from the top. B. The TCR binding site comprising three interacting domains of the TCR V regions. C. Combined pMHC-TCR binding site and the three “topes” that define interaction with self-MHC-molecule helices and peptide in the groove. Photo: Zlatko Dembic, IOB/UIO.



Melvin Cohn, Colin C. Anderson, Zlatko Dembic. The case for allele‐specific recognition by the TCR. Scandinavian Journal of Immunology, 2019 May 25.


Published Aug. 8, 2019 11:10 AM - Last modified Aug. 21, 2019 9:15 AM