HAEMONCHUS-CONTORTUS GA1 ANTIGENS - RELATED, PHOSPHOLIPASE C-SENSITIVE, APICAL GUT MEMBRANE-PROTEINS ENCODED AS A POLYPROTEIN AND RELEASED FROM THE NEMATODE DURING INFECTION

It was previously shown that the Haemonchus contortus apical gut surfa ce proteins p46, p52, and p100 induced protective immunity to challeng e infections in goats. sere, it is shown that the three proteins are a ll encoded by a single gene (GA1) sand initially expressed in adult pa rasites as a polyprotein (p100(GA1)), p46(GA1) and p52(GA1) are relate d proteins with 47% sequence identity, including a cysteine-containing region, which appears to confer secondary structure to these proteins , and a region with sequence similarity to bacterial Tolb proteins. GA 1 protein expression is regulated during the life cycle at the level o f transcript abundance. Only p52(GA1) has characteristics of a glycosy linositolphospholipid membrane-anchored protein. However, both p46(GA1 ) and p52(GA1) were released from tire gut membrane by phosphatidylino sitol specific-phospholipase C, suggesting that p46(GA1) membrane asso ciation depends on interactions with a glycosylinositolphospholipid gu t membrane protein. Finally, GA1 proteins occur in abomasal mucus of i nfected lambs, demonstrating possible presentation to the host immune system during H. contortus infection. The results identify multiple ch aracteristics of the GA1 proteins that should be considered for design of recombinant antigens for vaccine trials and that implicate a serie s of cellular processes leading to modification and expression of GA1 proteins at the nematode apical gut surface.