Binding of photoreactive lysozyme peptides to murine histocompatibility class II molecules.

Luescher, Immanuel F.; Allen, Paul M.; Unanue, Emil R.

doi:10.1073/pnas.85.3.871

Cited by 31 publications

(11 citation statements)

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“…Some of these studies have rightly stressed the fine specificity of MHC/peptide interaction which can occur, and have actually proposed predictive models of peptide structures with putative MHC-binding properties (deLisi & Berzovsky 1985, Rothbard & Taylor 1988. However, as has recently been reported, the equilibrium of this interaction can be profoundly altered by the presence of rather small modifying organic groups on the peptide (Luescher et al 1988). Similarly, we have recently shown that the immunogenicity of insulin can be profoundly altered at the level of antigen presentation by modification with a trinitrophenyl substituent (Wallace et al 1989).…”

Section: Interaction With the Mhcmentioning

confidence: 99%

The Biochemistry and Cell Biology of Antigen Processing

Chain

Kaye

Shaw

1988

Immunological Reviews

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Section: Interaction With the Mhcmentioning

confidence: 99%

The Biochemistry and Cell Biology of Antigen Processing

Chain

Kaye

Shaw

1988

Immunological Reviews

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“…When tested on cell membranes that contained class II MHC proteins, photoreactive conjugates of the hen egg white lysozyme (HEL) peptide from residues 46 to 61 labeled exclusively the a chain of I-Ak (13). Conversely, I-Ak purified in an equimolar solution of MEGA 8 and MEGA 9 detergents was labeled to similar extent on both chains.…”

mentioning

confidence: 99%

Phospholipids enhance the binding of peptides to class II major histocompatibility molecules.

Roof

Luescher²,

Unanue³

1990

Proc. Natl. Acad. Sci. U.S.A.

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The binding of a lysozyme and ovalbumin peptide to purified class II major histocompatibiity molecules in detergents was increased by the addition of certain lipids. Natural lipids from B lymphoma cells enhanced the binding and so did phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Phosphatidylethanolamine, sphingomyelin, and cholesterol had no effect. There was no major difference between the effects of a phospholipid and its lyso derivative. As studied with phosphatidylcholine, the increase in peptide binding was also dependent on the fatty acid composition of the lipid. (MHC) proteins (1,2). The extent of binding of peptides to histocompatibility molecules, which can be studied in detergent solutions (1-7), usually correlates with their immunogenicity in vivo (2-4). There are, however, indications that the interactions of peptides with class II MHC may be quantitatively different on live antigen-presenting cells. For example, the binding of antigenic peptides to class II MHC molecules on live cells was reported to be much faster than that found in solution (8-10). A similar result was found for the dissociation of peptides bound to the class II MHC molecules (11).We recently found that the labeling of class II MHC molecules to peptides containing a photoreactive compound was influenced by phospholipids, both in the extent as well as in the relative degree ofthe a or p chain labeling (12). When tested on cell membranes that contained class II MHC proteins, photoreactive conjugates of the hen egg white lysozyme (HEL) peptide from residues 46 to 61 labeled exclusively the a chain of I-Ak (13). Conversely, I-Ak purified in an equimolar solution of MEGA 8 and MEGA 9 detergents was labeled to similar extent on both chains. However, the addition of certain lysophospholipids resulted in strong binding, with lysophosphatidylcholine predominantly labeling the a chain and lysophosphatidylserine labeling the ,B chain. We concluded that class II MHC molecules contained dialyzable components required for their binding integrity and that, most likely, these components were lipids.Lipid-protein interactions are of critical importance in maintaining the biological activity of a number of membrane proteins (for review, see refs. 14-16). These interactions may have different degrees of specificity and often induce conformational changes in the protein critical for their function (14,(17)(18)(19)(20)(21)(22). Lipids, by interacting directly with the MHC protein or by changing the structure ofthe detergent micelles, may induce conformational changes reflected in the distal binding site of the protein (23,24). Consistent with this hypothesis are the observations indicating that class II MHC molecules reconstituted in lipid monolayers present peptides differently, depending on the lipid composition (25). Other studies have shown that treatment of antigen-presenting cells with purified phospholipase A2 or C, or with cerulenin, an antibiotic that interferes with lipid metabolism, greatly dimi...

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“…Although certain proteins are immunogenic in several mouse strains, often relatively non-overlapping portions of the molecule are the actual major immunogenic moieties in each of them [8-141. Even within one responding strain there is generally an association of an antigenic peptide with only one isotype of Ia molecule [4, 15,16]. In a recent study 60 out of 64 peptides have been shown to bind [I 77591 either IAd or IEd, but not both [17].When MHC restriction is degenerate, the different Ia reactivities mapped to overlapping, but yet distinct, regions of the peptide molecule and relatively subtle differences in peptide structure dramatically influenced the capacity of a peptide to interact with one but not another Ia specificity [lo, 161.…”

Section: Introductionmentioning

confidence: 99%

Competition among class II major histocompatibility molecules for presentation of tyrosine‐azobenzenearsonate occurs in vivo and in vitro

Baskar

Leskowitz

1990

Eur J Immunol

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We have compared by functional assays the relative preference among Ia molecules for their ability to present tyrosine-azobenzenearsonate (ABA-Tyr) to T cells. Immunization of B10.BR mice (IAk, IEk) with ABA-Tyr resulted in the induction of IAk-restricted T cells only. Immunization of B10.A(5R) mice (IAb, IEb/k) gave only IEb/k-restricted T cell clones even though IAb-restricted responses could be induced in C57BL/6 mice (IAb). These results indicated that IAk was preferred over IEk and IEb/k was preferred over IAb for presentation of ABA-Tyr. A comparison between IAk and IEb/k made by immunizing [B10.BR x B10.A(5R)]F1 mice (IAk, IEk, IAb, IEb/k), showed that IEb/k was favored over IAk. No IAb- or IEk-restricted response was seen. Further attempts were made to compare Ia preference for ABA-Tyr presentation by competitive inhibition assays. It could be shown that the presence of IEb/k molecules on an accessory cell interfered with the ability of IAb molecules on the same cell to present ABA-Tyr to an IAb-restricted T cell clone by direct competition. Such a competition was not observed between IAk and IEk. Finally, it could be shown that addition of ABA-Tyr inhibited the presentation of moth cytochrome-c peptide (81-103) by IEb/k but did not influence its presentation by IEk. From these functional studies we suggest that the binding affinity of ABA-Tyr with the Ia molecules will fall in the order: IEb/k greater than IAk greater than IAb greater than IEk.

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Binding of photoreactive lysozyme peptides to murine histocompatibility class II molecules.

Cited by 31 publications

References 14 publications

The Biochemistry and Cell Biology of Antigen Processing

The Biochemistry and Cell Biology of Antigen Processing

Phospholipids enhance the binding of peptides to class II major histocompatibility molecules.

Competition among class II major histocompatibility molecules for presentation of tyrosine‐azobenzenearsonate occurs in vivo and in vitro

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