Surface NKG2C Identifies Differentiated αβT-Cell Clones Expanded in Peripheral Blood

Abstract

T cells that express CD56 in peripheral blood of healthy humans represent a heterogeneous and poorly studied subset. In this work, we analyzed this subset for NKG2C expression. In both CD56⁺ and CD56^- subsets most of the NKG2C⁺ T cells had a phenotype of highly differentiated CD8⁺ TEMRA cells. The CD56⁺NKG2C⁺ T cells also expressed a number of NK cell receptors, such as NKG2D, CD16, KIR2DL2/DL3, and maturation marker CD57 more often than the CD56^-NKG2C⁺CD3⁺ cells. TCR β-chain repertoire of the CD3⁺CD56⁺NKG2C⁺ cell fraction was limited by the prevalence of one or several clonotypes which can be found within the most abundant clonotypes in total or CD8⁺ T cell fraction TCRβ repertoire. Thus, NKG2C expression in highly differentiated CD56⁺ T cells was associated with the most expanded αβ T cell clones. NKG2C⁺ T cells produced almost no IFN-γ in response to stimulation with HCMV pp65-derived peptides. This may be partially due to the high content of CD45RA⁺CD57⁺ cells in the fraction. CD3⁺NKG2C⁺ cells showed signs of activation, and the frequency of this T-cell subset in HCMV-positive individuals was positively correlated with the frequency of NKG2C⁺ NK cells that may imply a coordinated in a certain extent development of the NKG2C⁺ T and NK cell subsets under HCMV infection.

Keywords: NKG2C; NKT-like cells; T cell differentiation; TCR repertoire; cytomegalovirus infection.