Monoclonal TCR-Vbeta13.1+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin.
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.
Garrido
Pilar
P
Servicio de Hematología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Ruiz-Cabello
Francisco
F
Bárcena
Paloma
P
Sandberg
Yorick
Y
Cantón
Julia
J
Lima
Margarida
M
Balanzategui
Ana
A
González
Marcos
M
López-Nevot
Miguel Angel
MA
Langerak
Anton W
AW
García-Montero
Andrés C
AC
Almeida
Julia
J
Orfao
Alberto
A
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*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta