MHC CLASS-I MOLECULES ARE AN ESSENTIAL CELL-SURFACE COMPONENT INVOLVED IN THEILERIA-PARVA SPOROZOITE BINDING TO BOVINE LYMPHOCYTES

The major histocompatibility complex (MHC) class I molecules are ubiqu itous cell surface molecules involved in the cell-mediated immune resp onse, We show here, using a number of different, independent approache s, that these proteins are an essential component of the host cell sur face receptor involved in Theileria parva sporozoite invasion, Monoclo nal antibodies (mAbs) reactive with common determinants on MHC class I molecules and with beta-2 microglobulin inhibited sporozoite entry by specifically preventing the initial binding event, However, in experi ments using lymphocytes from heterozygous cattle in which at least fou r MHC class I gene products are expressed, mAbs which reacted with onl y one of these products did not inhibit entry, Using a series of bovin e deletion mutant cell lines from which one or both MHC class I haplot ypes had been lost, sporozoite binding and entry clearly correlated wi th the level of class I surface expression, While the level of sporozo ite entry into cells in which one of the MHC class I haplotypes was lo st was only slightly lower than into the parent cells, in a double del etion cell line having less than 5 % of the class I expression of the parent cells the level of infection was only 4.3 % of that into the pa rent cells, Furthermore, sporozoite entry into cells from a spontaneou sly arising mutant cell line exhibiting low levels of class I expressi on was correspondingly low, Treatment of lymphocytes with IL-2 produce d a significant increase in host cell susceptibility and sporozoite en try and this increase correlated with either an increase in the number of target molecules per host cell, or in the binding of bovine MHC cl ass I molecules to the mAbs, In particular, a significant increase in the level of reactivity with mAb W6/32 was observed, Lastly, we show t hat parasite entry can be competitively inhibited with an isolated spo rozoite surface protein, p67. However, p67 binds weakly to lymphocyte surface molecules and initial attempts to use p67 to isolate the relev ant host cell molecule(s) have not been successful.