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Extended repertoire of permissible peptide ligands for HLA-B*2702

Raghavan, Malini and Lebrón, José A. and Johnson, Jennifer L. and Bjorkman, Pamela J. (1996) Extended repertoire of permissible peptide ligands for HLA-B*2702. Protein Science, 5 (10). pp. 2080-2088. ISSN 0961-8368. PMCID PMC2143273. doi:10.1002/pro.5560051014.

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Recognition of self peptides bound to the class I major histocompatibility complex molecule HLA-B27 is thought to trigger proliferation of autoreactive T cells and result in autoimmune arthritic diseases. Previous work from other laboratories established that a predominant feature of endogenous peptides eluted from purified B27 is an arginine at position 2. We studied the binding of peptides containing both natural and unnatural amino acids by the subtype HLA-B*2702, with the goal of gaining insight into peptide binding by this B27 subtype that is associated with susceptibility to arthritic disease. A soluble form of B*2702 was depleted of endogeneous peptides. We tested the binding of peptides substituted with cysteine, homocysteine, or an α-amino-ϵ-mercapto hexanoic acid side chain (Amh) instead of the naturally occurring arginine at position 2, to determine whether the peptide sulfhydryl residue could be covalently linked to cysteine 67 in the B*2702 binding cleft. Although none of the altered peptide sequences bound covalently to B*2702, the affinities of the homocysteine- and Amh-substituted peptides were close to that of the native peptide sequence. Substitutions at position 2 with other side chains, such as glutamine and methionine, also resulted in peptides that bound with only slightly reduced affinity. These results demonstrate that peptide side chains other than arginine at position 2 can be accomodated within the B*2702 peptide binding site with only minor reductions in affinity. This extended repertoire of permissible B27-binding peptides should be taken into account for a consideration of disease-associated peptide sequences.

Item Type:Article
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URLURL TypeDescription CentralArticle
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1996 The Protein Society. Received June 25, 1996; Accepted July 19, 1996. This work was supported by a grant from the Arthritis Foundation (P.J.B.), a postdoctoral fellowship from the Cancer Research Institute (M.R.), and a predoctoral fellowship from the Ford Foundation (J.A.L.). We thank Dennis Dougherty and Steve Mayo for help with amino acid and peptide synthesis.
Funding AgencyGrant Number
Arthritis FoundationUNSPECIFIED
Cancer Research InstituteUNSPECIFIED
Ford FoundationUNSPECIFIED
Issue or Number:10
PubMed Central ID:PMC2143273
Record Number:CaltechAUTHORS:20170406-075420581
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Official Citation:Raghavan, M., Lebrón, J. A., Johnson, J. L. and Bjorkman, P. J. (1996), Extended repertoire of permissible peptide ligands for HLA-B*2702. Protein Science, 5: 2080–2088. doi:10.1002/pro.5560051014
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75777
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 15:58
Last Modified:15 Nov 2021 16:36

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