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

Monoclonal TCR alpha beta(+)/CD4(+) T-large granular lymphocyte (T-LGL) lymphocytosis is a T-cell disorder with a restricted TCR-V beta repertoire. In the present study we explored the potential association between the expanded TCR-Vp families, the CDR3 sequences of the TCR-V beta gene, and the HLA genotype of patients with monoclonal TCR alpha beta(+)/CD4(+) T-LGL lymphocytosis. For that purpose, 36 patients with monoclonal TCR alpha beta(+)/CD4(+) T-LGL lymphocytosis (15 TCR-V beta 13.1 versus 21 non-TCR-V beta 13.1) were selected. For each patient, both the HLA (class I and 11) genotype and the DNA sequences of the VDJ-rearranged TCR-V beta were analyzed. Our results show a clear association between the TCR-V beta repertoire and the HLA genotype, all TCR-V beta 13.1(+) cases being HLA-DRB1 -0701 (P =.004). Interestingly, the HLA-DR7/TCR-V beta 13.1-restricted T-cell expansions displayed a highly homogeneous and strikingly similar TCR arising from the use of common TCR-Vp gene segments, which shared (1) unique CDR3 structural features with a constantly short length, (2) similar combinatorial gene rearrangements with frequent usage of the J beta 1.1 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.