Proteome Analysis of Human CD56 NK Cells Reveals a Homogeneous Phenotype Surprisingly Similar to CD56 NK Cells

NK cells lacking CD56 (CD56 ) were first identified in chronic HIV-1 infection. However, CD56 NK cells also exist in healthy individuals, albeit in significantly lower numbers. Here, we provide an extensive proteomic characterisation of human CD56 peripheral blood NK cells of healthy donors and compare them to their CD56 and CD56 counterparts. Unbiased large-scale surface receptor profiling clustered CD56 cells as part of the main NK cell compartment and indicated an overall CD56 -like phenotype. Total proteome analyses of CD56 NK cells further confirmed their similarity with CD56 NK cells, and revealed a complete cytolytic inventory with high levels of perforin and granzyme H and M. In the present study, twelve proteins discriminated CD56 NK cells from CD56 NK cells with nine up-regulated and three down-regulated proteins in the CD56 NK cell population. Those proteins were functionally related to lytic granule composition and transport, interaction with the extracellular matrix, DNA transcription or repair, and proliferation. Corroborating these results, CD56 NK cells showed modest cytotoxicity, degranulation, and IFN-ɣ secretion as compared to CD56 NK cells. In conclusion, CD56 NK cells constitute functionally competent cells sharing many features of bona fide CD56 NK cells in healthy individuals, but with some distinct characteristics.