title: High-throughput sequencing reveals an altered T cell repertoire in X-linked agammaglobulinemia.
abstract: 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.
authors.affiliation: Montefiore Medical Center, Bronx, NY, United States.
authors.forename: Manish
authors.initials: M
authors.lastname: Ramesh
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Noa
authors.initials: N
authors.lastname: Simchoni
authors.affiliation: Adaptive Biotech, Seattle, WA, United States.
authors.forename: David
authors.initials: D
authors.lastname: Hamm
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Pediatrics, The Immunology Institute, Box 1089, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, United States.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cunningham-Rundles
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007223:Infant; D008297:Male; D008875:Middle Aged; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D055815:Young Adult
chemical_list: D007135:Immunoglobulin Variable Region; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D004247:DNA
keywords: Amino acid sequence; High throughput sequencing; Junctional diversity; T cell receptor; XLA