Human platelet antigen ( HPA )‐1a peptides do not reliably suppress anti‐ HPA ‐1a responses using a humanized severe combined immunodeficiency ( SCID ) mouse model

Summary Fetal and neonatal alloimmune thrombocytopenia ( FNAIT ) occurs most frequently when human platelet antigen ( HPA )‐1a‐positive fetal platelets are destroyed by maternal HPA ‐1a immunoglobulin ( Ig)G antibodies. Pregnancies at risk are treated by administration of high‐dose intravenous Ig ( IVIG ) to women, but this is expensive and often not well tolerated. Peptide immunotherapy may be effective for ameliorating some allergic and autoimmune diseases. The HPA ‐1a/1b polymorphism is L eu/ P ro33 on β3 integrin ( CD 61), and the anti‐ HPA ‐1a response is restricted to HPA ‐1b1b and HLA ‐ DRB 3*0101‐positive pregnant women with an HPA ‐1a‐positive fetus. We investigated whether or not HPA ‐1a antigen‐specific peptides that formed the T cell epitope could reduce IgG anti‐ HPA ‐1a responses, using a mouse model we had developed previously. Peripheral blood mononuclear cells ( PBMC ) in blood donations from HPA ‐1a‐immunized women were injected intraperitoneally (i.p.) into severe combined immunodeficient ( SCID ) mice with peptides and HPA ‐1a‐positive platelets. Human anti‐ HPA ‐1a in murine plasma was quantitated at intervals up to 15 weeks. HPA ‐1a‐specific T cells in PBMC were identified by proliferation assays. Using PBMC of three donors who had little T cell reactivity to HPA ‐1a peptides in vitro , stimulation of anti‐ HPA ‐1a responses by these peptides occurred in vivo . However, with a second donation from one of these women which, uniquely, had high HPA ‐1a‐specific T cell proliferation in vitro , marked suppression of the anti‐ HPA ‐1a response by HPA ‐1a peptides occurred in vivo . HPA ‐1a peptide immunotherapy in this model depended upon reactivation of HPA ‐1a T cell responses in the donor. For FNAIT , we suggest that administration of antigen‐specific peptides to pregnant women might cause either enhancement or reduction of pathogenic antibodies.