Bovine Neonatal Pancytopenia (BNP), a fatal bleeding syndrome of neonatal calves, is caused
by maternal alloantibodies absorbed from colostrum and is characterized by lymphocytopenia,
thrombocytopenia and bone marrow hypoplasia. An inactivated viral vaccine is the likely source of
alloantigens inducing BNP-associated alloantibodies in the dam. In this study the specificity of BNP
alloantibodies was assessed and was linked to the pathology of BNP. We demonstrated that Major
Histocompatibility Complex class I (MHC I) and Very Late Antigen-3, an integrin α3/β1 heterodimer,
were the major targets of BNP alloantibodies. However, alloantibody binding to various bovine
cell types correlated with MHC I expression, rather than integrin β1 or α3 expression. Likewise,
alloantibody-dependent complement-mediated cell lysis correlated strongly with MHC I expression.
Examination of several tissues of third trimester bovine foetuses revealed that cells, shown to be
affected in calves with BNP, were characterized by high MHC class I expression and high levels of
alloantibody binding. We conclude that in spite of the heterogeneous specificity of BNP associated
maternal alloantibodies, MHC I-specific antibodies mediate the pathogenicity of BNP in the calf and
that cells with high MHC I expression were preferentially affected in BNP.