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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4890-4898. Prepublished online as a Blood First Edition Paper on February 15, 2007; DOI 10.1182/blood-2006-05-022277. This Article Full Text (PDF) All Versions of this Article: blood-2006-05-022277v1 109/11/4890    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Garrido, P. Articles by Orfao, A. Search for Related Content PubMed PubMed Citation Articles by Garrido, P. Articles by Orfao, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 11, 2006 Accepted February 12, 2007 Monoclonal TCR-V13.1+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin Pilar Garrido, Francisco Ruiz-Cabello, Paloma Barcena, Yorick Sandberg, Julia Canton, Margarida Lima, Ana Balanzategui, Marcos Gonzalez, Miguel Angel Lopez-Nevot, Anton W Langerak, Andres C Garcia-Montero, Julia Almeida, and Alberto Orfao* Servicio de Hematologia, Hospital Universitario Virgen de las Nieves, Granada, Spain Servicio de Analisis Clinicos, Hospital Universitario Virgen de las Nieves, Granada, Spain Servicio de Citometria & Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain Department of Immunology, Erasmus MC, Rotterdam, Netherlands Servicio de Hematologia, Hospital Geral de Santo Antonio, Porto, Portugal Instituto de Biologia Molecular y Celular del Cancer, Centro de Investigacion del Cancer/IBMCC (CSIC-USAL), Salamanca, Spain Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain * Corresponding author; email: orfao{at}usal.es. Monoclonal TCR+/CD4+ T-large granular lymphocyte (LGL) lymphocytosis is a T-cell disorder with a restricted TCR-V repertoire. In the present study we explored the potential association between the expanded TCR-V families, the CDR3 sequences of the TCR-V gene and the HLA genotype of patients with monoclonal TCR+/CD4+ T-LGL lymphocytosis. For that purpose, 36 patients with monoclonal TCR+/CD4+ T-LGL lymphocytosis (15 TCR-V13.1 versus 21 non-TCR-V13.1) were selected. For each patient, both the HLA (class I and II) genotype and the DNA sequences of the VDJ rearranged TCR-V were analyzed. Our results show a clear association between the TCR-V repertoire and the HLA genotype, all TCR-V13.1+ cases being HLA-DRB1*0701 (p=0.004). Interestingly, the HLA-DR7/TCR-V 13.1 restricted T-cell expansions displayed a highly homogeneous and strikingly similar TCR, arising from the use of common TCR-V gene segments which shared: 1) unique CDR3 structural features with a constantly short length, 2) similar combinatorial gene rearrangements with frequent usage of the J1.1 gene, and 3) a homologue consensus protein sequence at recombination junctions. Overall, these findings strongly support the existence of a common antigen-driven origin for monoclonal CD4+ T-LGL lymphocytosis, with the identification of the exact peptides presented to the expanded T-cells deserving further investigations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020