Molecular determinants of peptide binding to two common rhesus macaque major histocompatibility complex class II molecules

J. L. Dzuris, J. Sidney, H. Horton, R. Correa, D. Carter, R. W. Chesnut, David Watkins, A. Sette

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)10958-10968
Number of pages11
JournalJournal of Virology
Volume75
Issue number22
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

Fingerprint

Dichlororibofuranosylbenzimidazole
major histocompatibility complex
Macaca mulatta
Major Histocompatibility Complex
peptides
Peptides
epitopes
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Macaca
HLA-DR Antigens
Epitopes
rev Gene Products
HIV
HLA-DRB1 Chains
antigen detection
T-Lymphocyte Epitopes
binding capacity
interferon-gamma
Interferon-gamma

ASJC Scopus subject areas

  • Immunology

Cite this

Molecular determinants of peptide binding to two common rhesus macaque major histocompatibility complex class II molecules. / Dzuris, J. L.; Sidney, J.; Horton, H.; Correa, R.; Carter, D.; Chesnut, R. W.; Watkins, David; Sette, A.

In: Journal of Virology, Vol. 75, No. 22, 15.11.2001, p. 10958-10968.

Research output: Contribution to journalArticle

Dzuris, J. L. ; Sidney, J. ; Horton, H. ; Correa, R. ; Carter, D. ; Chesnut, R. W. ; Watkins, David ; Sette, A. / Molecular determinants of peptide binding to two common rhesus macaque major histocompatibility complex class II molecules. In: Journal of Virology. 2001 ; Vol. 75, No. 22. pp. 10958-10968.
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AU - Sidney, J.

AU - Horton, H.

AU - Correa, R.

AU - Carter, D.

AU - Chesnut, R. W.

AU - Watkins, David

AU - Sette, A.

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