title: Monoclonal TCR-Vbeta13.1+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin.
abstract: Monoclonal TCRalphabeta(+)/CD4+ T-large granular lymphocyte (T-LGL) lymphocytosis is a T-cell disorder with a restricted TCR-Vbeta repertoire. In the present study we explored the potential association between the expanded TCR-Vbeta families, the CDR3 sequences of the TCR-Vbeta gene, and the HLA genotype of patients with monoclonal TCRalphabeta(+)/CD4+ T-LGL lymphocytosis. For that purpose, 36 patients with monoclonal TCRalphabeta(+)/CD4+ T-LGL lymphocytosis (15 TCR-Vbeta13.1 versus 21 non-TCR-Vbeta13.1) were selected. For each patient, both the HLA (class I and II) genotype and the DNA sequences of the VDJ-rearranged TCR-Vbeta were analyzed. Our results show a clear association between the TCR-Vbeta repertoire and the HLA genotype, all TCR-Vbeta13.1(+) cases being HLA-DRB1*0701 (P = .004). Interestingly, the HLA-DR7/TCR-Vbeta13.1-restricted T-cell expansions displayed a highly homogeneous and strikingly similar TCR arising from the use of common TCR-Vbeta gene segments, which shared (1) unique CDR3 structural features with a constantly short length, (2) similar combinatorial gene rearrangements with frequent usage of the Jbeta1.1 gene, and (3) a homolog 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.
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Cabello
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.forename: Yorick
authors.initials: Y
authors.lastname: Sandberg
authors.forename: Julia
authors.initials: J
authors.lastname: Cantón
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Andrés C
authors.initials: AC
authors.lastname: García-Montero
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015704:CD4 Antigens / Q000096:biosynthesis*; D016827:CD8 Antigens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008218:Lymphocytosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta