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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1723-1729
IMMUNOBIOLOGY
Analysis of natural killer cells in TAP2-deficient patients:
expression of functional triggering receptors and evidence for the
existence of inhibitory receptor(s) that prevent lysis of normal
autologous cells
Massimo Vitale,
Jacques Zimmer,
Roberta Castriconi,
Daniel Hanau,
Lionel Donato,
Cristina Bottino,
Lorenzo Moretta,
Henri de la
Salle, and
Alessandro Moretta
From the Istituto Nazionale per la Ricerca sul Cancro,
Genova, the Dipartimento di Medicina Sperimentale, Università di
Genova, and the Istituto Giannina Gaslini, Genova, Italy; INSERM EP
99-08 Etablissement Francais du Sang-Alsace, Strasbourg, and Service de
Pediatrie, Hopital de Hautepierre, Strasbourg, France.
Natural killer (NK) cells are characterized by the ability to kill
cells that lack HLA class I molecules while sparing autologous normal
(HLA class I+) cells. However, patients with
transporter-associated antigen processing (TAP) deficiency, though
displaying strong reductions of HLA class I surface expression, in most
instances do not experience NK-mediated autoimmune phenomena. A
possible mechanism by which TAP / NK cells avoid
autoreactivity against autologous HLA class I-deficient cells could be
based on either quantitative or qualitative defects of surface
receptors involved in NK cell triggering. In this study we show that NK
cells derived from 2 patients with TAP2/ express normal
levels of all known triggering receptors. As revealed by the analysis
of polyclonal and clonal NK cells, these receptors display normal
functional capabilities and allow the killing of a panel of
NK-susceptible targets, including autologous B-LCLs. On the other hand,
TAP2/ NK cells were unable to kill either allogeneic
(HLA class I+) or autologous (HLA class I )
phytohemagglutinin (PHA) blasts even in the presence of anti-HLA class
I monoclonal antibody. These data suggest that TAP2/ NK
cells express still unknown inhibitory receptor(s) capable of
down-regulating the NK cell cytotoxicity on binding to surface ligand(s) expressed by T cell blasts. Functional analyses, both at the
polyclonal and at the clonal level, are consistent with the concept
that the putative inhibitory receptor is expressed by virtually all
TAP2/ NK cells, whereas it is present only in rare NK
cells from healthy persons. Another possibility would be that
TAP2/ NK cells are missing a still unidentified
triggering receptor involved in NK cell-mediated killing of PHA blasts.
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