TY  - JOUR
A1  - Madi, Asaf
A1  - Shifrut, Eric
A1  - Reich-Zeliger, Shlomit
A1  - Gal, Hilah
A1  - Best, Katharine
A1  - Ndifon, Wilfred
A1  - Chain, Benjamin
A1  - Cohen, Irun R.
A1  - Friedman, Nir
T1  - T-cell receptor repertoires share a restricted set of public and abundant CDR3 sequences that are associated with self-related immunity
Y1  - 2014/10/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1603 
EP  - 1612 
DO  - 10.1101/gr.170753.113 
VL  - 24 
IS  - 10 
UR  - http://genome.cshlp.org/content/24/10/1603.abstract 
N2  - The T-cell receptor (TCR) repertoire is formed by random recombinations of genomic precursor elements; the resulting combinatorial diversity renders unlikely extensive TCR sharing between individuals. Here, we studied CDR3β amino acid sequence sharing in a repertoire-wide manner, using high-throughput TCR-seq in 28 healthy mice. We uncovered hundreds of public sequences shared by most mice. Public CDR3 sequences, relative to private sequences, are two orders of magnitude more abundant on average, express restricted V/J segments, and feature high convergent nucleic acid recombination. Functionally, public sequences are enriched for MHC-diverse CDR3 sequences that were previously associated with autoimmune, allograft, and tumor-related reactions, but not with anti-pathogen-related reactions. Public CDR3 sequences are shared between mice of different MHC haplotypes, but are associated with different, MHC-dependent, V genes. Thus, despite their random generation process, TCR repertoires express a degree of uniformity in their post-genomic organization. These results, together with numerical simulations of TCR genomic rearrangements, suggest that biases and convergence in TCR recombination combine with ongoing selection to generate a restricted subset of self-associated, public CDR3 TCR sequences, and invite reexamination of the basic mechanisms of T-cell repertoire formation. 
ER  -