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 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 degrees C, but can be partially stabilized by addition of exogenous beta(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.
Gouttefangeas
C
C
Department of Immunology, Institute for Cell Biology, and Department of Transfusion Medicine, University Hospital, Tübingen, Germany.
Diehl
M
M
Keilholz
W
W
Hörnlein
R F
RF
Stevanović
S
S
Rammensee
H G
HG
D001792:Blood Platelets / Q000166:cytology / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015789:HLA-A2 Antigen / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008533:Megakaryocytes / Q000166:cytology / Q000276:immunology; D015539:Platelet Activation
D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens