Thrombocyte HLA molecules retain nonrenewable endogenous peptides of megakaryocyte lineage and do not stimulate direct allocytotoxicity in vitro

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 w hich fraction of these class I molecules represents integral membrane compo nents derived from the megakaryocyte-platelet lineage versus soluble plasma HLA molecules acquired by adsorption. Results of the present study show th at HLA-A2 ligands isolated from platelets possess the same peptide motif as described for HLA-A2-associated peptides obtained from nucleated cells. Se quencing of these platelet- derived peptides reveals that they originate ma inly from ubiquitously expressed proteins also present in the megakaryocyte -platelet lineage. Moreover, one of these peptides derives from the GPIX pr otein, which is specifically expressed by platelets and their precursors. P latelet HLA molecules are unstable in vitro at 37 degrees C, but can be par tially stabilized by addition of exogenous beta(2)-microglobulin and HLA cl ass I binding peptide, suggesting that platelets cannot load HLA molecules with endogenous peptides. In in vitro experiments platelets were used to st imulate peripheral blood mononuclear cells, No allospecific cytotoxicity wa s observed after primary stimulation, or secondary restimulation, with allo genic resting or activated platelets, even in the presence of additional th ird-party helper activity. These data indicate that HLA class I molecules f rom platelets cannot directly induce allogenic CD8(+) cytotoxic T-cell resp onse in vitro. (C) 2000 by The American Society of Hematology.