TY - JOUR
T1 - Control of antigen presentation by a single protease cleavage site
AU - Antoniou, Antony N.
AU - Blackwood, Sarah-Louise
AU - Mazzeo, Daniela
AU - Watts, Colin
N1 - Funding Information:
We thank Eric Hewitt for the YM 1148/9 to FK 1148/9 and YY 1165/6 to FK 1165/6 mutants, Andy Knight for LB27.4/11.3 transfectants, S. Amigorena and C. Bonnerot for FcγRIIB2-transfected IIA1.6 cells and help with preparation of B cell lysosomal fractions, P. Emsley and N. Isaacs for the TTCF coordinates, and our colleagues for helpful comments on the manuscript. This work was supported by a Wellcome Trust Program Grant (to C.W.). D.M. is supported by a European Union Training Grant.
PY - 2000/4/1
Y1 - 2000/4/1
N2 - Protein antigens require limited proteolytic processing to generate peptides for binding to class II MHC molecules, but the proteases and processing sites involved are largely unknown. Here we analyze the effect of eliminating the three major asparagine endopeptidase (AEP)-processing sites in the microbial antigen tetanus toxin C fragment. The mutant antigen is highly resistant to proteolysis by AEP and crude lysosomal extracts and is dramatically impaired in its ability to be processed and presented to T cells. Remarkably, processing at a single asparagine residue (1219) is obligatory for optimal presentation of many T cell epitopes in this antigen. These studies demonstrate that cleavage at a single processing site can be crucial for effective antigen presentation.
AB - Protein antigens require limited proteolytic processing to generate peptides for binding to class II MHC molecules, but the proteases and processing sites involved are largely unknown. Here we analyze the effect of eliminating the three major asparagine endopeptidase (AEP)-processing sites in the microbial antigen tetanus toxin C fragment. The mutant antigen is highly resistant to proteolysis by AEP and crude lysosomal extracts and is dramatically impaired in its ability to be processed and presented to T cells. Remarkably, processing at a single asparagine residue (1219) is obligatory for optimal presentation of many T cell epitopes in this antigen. These studies demonstrate that cleavage at a single processing site can be crucial for effective antigen presentation.
UR - http://www.scopus.com/inward/record.url?scp=0033696962&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80191-0
DO - 10.1016/S1074-7613(00)80191-0
M3 - Article
C2 - 10795737
AN - SCOPUS:0033696962
SN - 1074-7613
VL - 12
SP - 391
EP - 398
JO - Immunity
JF - Immunity
IS - 4
ER -
