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The Journal of Immunology, Vol 156, Issue 1 176-182, Copyright © 1996 by American Association of Immunologists


ARTICLES

Amino acid residues on the I-Ak alpha-chain required for the binding and stability of two antigenic peptides

CA Nelson, N Viner, S Young, S Petzold, C Benoist, D Mathis and ER Unanue
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.

The class II molecules of the MHC bind processed Ag fragments (peptides) for presentation to T cells, but the role of individual MHC residues in binding these peptides has not been entirely defined. A panel of 27 mutant I-Ak transfectants was analyzed for the capacity to bind 2 unrelated peptides. The main peptides examined were hen egg lysozyme residues 48-62 and heat shock protein (hsp70) to residues 28- 41. Alanine substitutions of sites in the alpha-helical region of the I- Ak alpha-chain altered the ability of this class II protein to bind both peptides. Of the 27 substitutions tested, nine caused a decrease in peptide binding while only three caused an increase in peptide binding. The stabilities of these altered I-Ak-peptide complexes were also examined on SDS-Page. Complexes with lowered stabilities were observed after only four substitutions, and in all four cases this loss of stability was accompanied by a loss in hen egg lysozyme or hsp70 peptide-binding ability. Further, three of these residues lie in the short extended strand at the N terminus of the alpha-helix of the alpha 1 domain, suggesting that this region of I-Ak molecule may be critical for the formation of stable peptide-MHC complexes.


This article has been cited by other articles:


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Proc. Natl. Acad. Sci. USAHome page
R. R. Latek, S. J. Petzold, and E. R. Unanue
Hindering auxiliary anchors are potent modulators of peptide binding and selection by I-Ak class II molecules
PNAS, September 29, 2000; (2000) 210384197.
[Abstract] [Full Text]


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Am. J. Pathol.Home page
E. R. Unanue
Chemical Features of Peptide Selection by the Class II Histocompatibility Molecules
Am. J. Pathol., March 1, 1999; 154(3): 651 - 664.
[Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
R. R. Latek, S. J. Petzold, and E. R. Unanue
Hindering auxiliary anchors are potent modulators of peptide binding and selection by I-Ak class II molecules
PNAS, October 10, 2000; 97(21): 11460 - 11465.
[Abstract] [Full Text] [PDF]




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