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Updated: Mar 31, 2026
Expansion, Purification, and Functional Assessment of Human Peripheral Blood NK Cells
Published on: February 2, 2011
Polyclonal Expansion of NKG2C(+) NK Cells in TAP-Deficient Patients
Vivien Béziat1, Marwan Sleiman2, Jodie P Goodridge3
1Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet , Stockholm , Sweden ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163 , Paris , France ; Imagine Institute, University Paris Descartes , Paris , France.
Insights
Adaptive natural killer (NK) cell expansion, marked by NKG2C(+) cells, occurs even without normal HLA class I levels in transporter associated with antigen presentation (TAP) deficiency. These NK cells remain responsive, suggesting a role in antiviral immunity.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Adaptive natural killer (NK) cell responses are crucial for controlling viral infections like human cytomegalovirus (CMV).
- These responses involve the expansion of NKG2C(+) NK cells, which express inhibitory killer-cell immunoglobulin-like receptors (KIRs) that recognize self-HLA class I molecules.
Purpose of the Study:
- To investigate the role of HLA class I in the expansion of NKG2C(+) NK cells during adaptive NK cell responses.
- To understand the functional characteristics of NKG2C(+) NK cells in the absence of normal HLA class I expression.
Main Methods:
- Analysis of NKG2C(+) NK cell populations in patients with transporter associated with antigen presentation (TAP) deficiency.
- Assessment of KIR profiles and responsiveness to target cells in TAP-deficient patients.
- Functional assays involving agonistic stimulation of NKG2C on NK cells from TAP-deficient patients.
Main Results:
- NKG2C(+) NK cells expand in TAP-deficient patients with severely reduced HLA class I levels.
- Expanded NKG2C(+) NK cells in TAP-deficient patients show a polyclonal KIR profile and are hyporesponsive to HLA class I-negative targets.
- Despite hyporesponsiveness, NKG2C stimulation elicits degranulation and cytokine production in these cells.
Conclusions:
- HLA class I interactions shape KIR repertoire in adaptive NK cells but are not essential for NKG2C(+) NK cell expansion.
- NKG2C-responsive adaptive NK cells can emerge independently of normal HLA class I expression.
- The presence of these adaptive NK cells may contribute to effective antiviral immunity in TAP-deficient individuals.
Abstract:
Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C(+) NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C(+) NK cell expansions. We demonstrate the expansion of NKG2C(+) NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C(+) NK cell populations in TAP-deficient patients display a polyclonal KIR profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR repertoire of expanding NKG2C(+) NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C(+) NK cell expansions to occur. The emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to antiviral immunity and potentially explain these patients' low incidence of severe viral infections.
