High-throughput sequencing reveals an altered T cell repertoire in X-linked agammaglobulinemia.
To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.
['Ramesh|Manish|M|', 'Simchoni|Noa|N|', 'Hamm|David|D|', 'Cunningham-Rundles|Charlotte|C|']
D000293:Adolescent D000328:Adult D000361:Agammaglobulinemia D001402:B-Lymphocytes D016022:Case-Control Studies D002648:Child D002675:Child, Preschool D004247:DNA D040181:Genetic Diseases, X-Linked D059014:High-Throughput Nucleotide Sequencing D006801:Humans D007135:Immunoglobulin Variable Region D007223:Infant D008297:Male D008875:Middle Aged D017260:Receptor-CD3 Complex, Antigen, T-Cell D011948:Receptors, Antigen, T-Cell D013601:T-Lymphocytes D055815:Young Adult
T cell receptor XLA Amino acid sequence High throughput sequencing Junctional diversity