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Journal of Virology, November 2001, p. 10958-10968, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10958-10968.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Molecular Determinants of Peptide Binding to Two Common Rhesus Macaque Major Histocompatibility Complex Class II Molecules

John L. Dzuris,1 John Sidney,1 Helen Horton,2 Rose Correa,1 Donald Carter,2 Robert W. Chesnut,1 David I. Watkins,2 and Alessandro Sette1,*

Epimmune, Inc., San Diego, California 92121,1 and Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 537152

Received 5 July 2001/Accepted 13 August 2001

Major histocompatibility complex class II molecules encoded by two common rhesus macaque alleles Mamu-DRB1*0406 and Mamu-DRB*w201 have been purified, and quantitative binding assays have been established. The structural requirements for peptide binding to each molecule were characterized by testing panels of single-substitution analogs of the two previously defined epitopes HIV Env242 (Mamu-DRB1*0406 restricted) and HIV Env482 (Mamu-DRB*w201 restricted). Anchor positions of both macaque DR molecules were spaced following a position 1 (P1), P4, P6, P7, and P9 pattern. The specific binding motif associated with each molecule was distinct, but largely overlapping, and was based on crucial roles of aromatic and/or hydrophobic residues at P1, P6, and P9. Based on these results, a tentative Mamu class II DR supermotif was defined. This pattern is remarkably similar to a previously defined human HLA-DR supermotif. Similarities in binding motifs between human HLA and macaque Mamu-DR molecules were further illustrated by testing a panel of more than 60 different single-substitution analogs of the HLA-DR-restricted HA 307-319 epitope for binding to Mamu-DRB*w201 and HLA-DRB1*0101. The Mamu-DRB1*0406 and -DRB*w201 binding capacity of a set of 311 overlapping peptides spanning the entire simian immunodeficiency virus (SIV) genome was also evaluated. Ten peptides capable of binding both molecules were identified, together with 19 DRB1*0406 and 43 DRB*w201 selective binders. The Mamu-DR supermotif was found to be present in about 75% of the good binders and in 50% of peptides binding with intermediate affinity but only in approximately 25% of the peptides which did not bind either Mamu class II molecule. Finally, using flow cytometric detection of antigen-induced intracellular gamma interferon, we identify a new CD4+ T-lymphocyte epitope encoded within the Rev protein of SIV.

* Corresponding author. Mailing address: Epimmune Inc., 5820 Nancy Ridge Dr., San Diego, CA 92121. Phone: (858) 860-2500. Fax: (858) 860-2600. E-mail: asette{at}epimmune.com.

Journal of Virology, November 2001, p. 10958-10968, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.10958-10968.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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