Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3168-3175
Thrombocyte HLA molecules retain nonrenewable endogenous peptides
of megakaryocyte lineage and do not stimulate direct allocytotoxicity
in vitro
Cécile Gouttefangeas,
Marianne Diehl,
Wieland Keilholz,
Rainer Frank Hörnlein,
Stefan Stevanovi
, and
Hans-Georg Rammensee
From the Department of Immunology, Institute for Cell Biology, and
Department of Transfusion Medicine, University Hospital,
Tübingen, Germany.
The origin and the function of HLA class I molecules present on the
surface of human platelets are still unclear. In particular, it is
controversial which fraction of these class I molecules represents
integral membrane components derived from the megakaryocyte-platelet lineage versus soluble plasma HLA molecules acquired by adsorption. Results of the present study show that HLA-A2 ligands isolated from
platelets possess the same peptide motif as described for HLA-A2-associated peptides obtained from nucleated cells. Sequencing of
these platelet-derived peptides reveals that they originate mainly from
ubiquitously expressed proteins also present in the megakaryocyte-platelet lineage. Moreover, one of these peptides derives
from the GPIX protein, which is specifically expressed by platelets and
their precursors. Platelet HLA molecules are unstable in vitro at
37°C, but can be partially stabilized by addition of exogenous
2-microglobulin and HLA class I binding peptide,
suggesting that platelets cannot load HLA molecules with endogenous
peptides. In in vitro experiments platelets were used to stimulate
peripheral blood mononuclear cells. No allospecific cytotoxicity was
observed after primary stimulation, or secondary restimulation, with
allogenic resting or activated platelets, even in the presence of
additional third-party helper activity. These data indicate that HLA
class I molecules from platelets cannot directly induce allogenic
CD8+ cytotoxic T-cell response in vitro.
