title: VDJ recombinase-mediated TCR β locus gene usage and coding joint processing in peripheral T cells during perinatal and pediatric development.
abstract: The generation of TCR proteins is the result of V(D)J recombinase-mediated genomic rearrangements at recombination signal sequences (RSS) in human lymphocytes. V(D)J recombinase can also mediate rearrangements at nonimmune or "cryptic" RSS in normal and leukemic human peripheral T cells. We previously demonstrated age- and gender-specific developmental differences in V(D)J coding joint processing at cryptic RSS within the HPRT locus in peripheral T cells from healthy children (Murray et al. 2006. J. Immunol. 177: 5393-5404). In this study, we investigated developmentally specific V(D)J recombinase TCRβ immune gene rearrangements and coding joint processing at RSS in peripheral T cells in the same pediatric population. This approach provided a unique opportunity to investigate site-specific V(D)J recombinase rearrangements and coding joint processing at immune and nonimmune genes from the same individual T cell population. We determined the genomic sequence of 244 TCRβ coding junctions from 112 (63 male, 49 female) subjects from the late stages of fetal development through 9 y of age. We observed both age- and gender-specific V(D)J recombinase-mediated TCRβ gene usage and coding joint processing at immune RSS. To the best of our knowledge, these data represent the first description of age- and gender-specific developmental differences in TCR gene usage and coding joint processing that could directly influence TCR diversity and immune specificity. It will be important for future studies to ascertain the mechanistic etiology of these developmental and gender differences in TCR diversity and specificity, as well as their importance with respect to the age and gender risks for infectious and autoimmune diseases in humans.
authors.affiliation: Department of Pediatrics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Murray
authors.forename: Terri
authors.initials: T
authors.lastname: Messier
authors.forename: Jami
authors.initials: J
authors.lastname: Rivers
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Neill
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Walker
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Vacek
authors.forename: Barry A
authors.initials: BA
authors.lastname: Finette
mesh_terms: D002648:Child; D015331:Cohort Studies; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology*; D056426:Genetic Loci / Q000276:immunology*; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology*; D045567:VDJ Recombinases / Q000502:physiology*
chemical_list: D007133:Immunoglobulin Joining Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D045567:VDJ Recombinases