Amino-acid enrichment in TCRs

In 2008, we examined a limited set ot then available crystallographic data from TCR/peptide interfaces:

Latter analysis of a large database of TCR sequences did not reveal such bias, but did not distinguish peptide contacts.

Y. Elhanati, A. Murugan, C.G. Callan,T. Mora, & A.M. Walczak, PNAS 111, 9875 (2013) (offlline)

Self-reactive TCR (implicated in autoimmune disease) are enriched in stronger binding amino-acids:

B.D. Stadinski, K. Shekhar, ..., A.K. Chakraborty & E. Huseby, Nature Immunology 17, 946 (2016)

 

Interpreting and accounting for nonuniform TCR contact profiles

Hanrong Chen, A.K. Chakraborty, & M. Kardar, (2018) (offlline)

(1)      vs. (2)

While the mean energy is the same in the two cases, the variance in energy is different.

The (experimentally seen) enrichment of weak amino-acids at sites 6 & 7, is observed in model (2) but not (1).

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Next (Thymic selection) Outline Adaptive Immunity Thymic Selection Amino acid enrichment Quorum sensing Affinity Maturation Broadly neutralizing Abs EMF dynamics Summary