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Monoclonal TCR-Vβ13.1+/CD4+/NKa +/CD8-/+dim T-LGL lymphocytosis: Evidence for an antigen-driven chronic T-cell stimulation origin

AuthorsGarrido, Pilar; Bárcena, Paloma; Balanzategui, Ana; González, Marcos ; García-Montero, Andrés ; Almeida, Julia ; Orfao, Alberto
Issue Date2007
PublisherAmerican Society of Hematology
CitationBlood 109(11): 4890-4898 (2007)
AbstractMonoclonal TCRαβ+/CD4+ T-large granular lymphocyte (T-LGL) lymphocytosis is a T-cell disorder with a restricted TCR-Vβ repertoire. In the present study we explored the potential association between the expanded TCR-Vβ families, the CDR3 sequences of the TCR-Vβ gene, and the HLA genotype of patients with monoclonal TCRαβ+/CD4+ T-LGL lymphocytosis. For that purpose, 36 patients with monoclonal TCRαβ+/CD4 + T-LGL lymphocytosis (15 TCR-Vβ13.1 versus 21 non-TCR-Vβ13.1) were selected. For each patient, both the HLA (class I and II) genotype and the DNA sequences of the VDJ-rearranged TCR-Vβ were analyzed. Our results show a clear association between the TCR-Vβ repertoire and the HLA genotype, all TCR-Vβ13.1+ cases being HLADRB1* 0701 (P = .004). Interestingly, the HLA-DR7/TCR-Vβ13.1- restricted T-cell expansions displayed a highly homogeneous and strikingly similar TCR arising from the use of common TCR-Vβ gene segments, which shared (1) unique CDR3 structural features with a constantly short length, (2) similar combinatorial gene rearrangements with frequent usage of the Jβ1.1 gene, and (3) a homolog consensus protein sequence at recombination junctions. Overall, these findings strongly support the existence of a common antigendriven origin for monoclonal CD4+ T-LGL lymphocytosis, with the identification of the exact peptides presented to the expanded T cells deserving further inves tigations.
Identifiersdoi: 10.1182/blood-2006-05-022277
issn: 0006-4971
e-issn: 1528-0020
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