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Effects of Peptide Length and Composition on Binding to an Empty Class I MHC Heterodimer

Fahnestock, Margaret L. and Johnson, Jennifer L. and Feldman, R. M. Renny and Tsomides, Theodore J. and Mayer, John and Narhi, Linda O. and Bjorkman, Pamela J. (1994) Effects of Peptide Length and Composition on Binding to an Empty Class I MHC Heterodimer. Biochemistry, 33 (26). pp. 8149-8158. ISSN 0006-2960. https://resolver.caltech.edu/CaltechAUTHORS:20170406-135433740

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Abstract

Class I major histocompatibility complex (MHC) proteins present peptide antigens to T cells during the immune response against viruses. Peptides are loaded into newly synthesized class I heterodimers in the endoplasmic reticulum such that most or all cell surface class I molecules contain peptides derived from endogenous or foreign proteins. We previously reported the assembly of empty heterodimers of the murine class I MHC molecule H-2K^d, from denatured heavy and light chains from which endogenous peptides had been removed [Fahnestock et al. (1992) Science 258,1658-16621. Here we measure thermal stability profiles of empty versus peptide-filled molecules and compare the effects of human versus murine light chains on the overall stability of the K^d heterodimer. The majority of empty heterodimers are stable at 37 °C regardless of the species of light chain, indicating that our previous report of the unexpectedly high thermal stability was an intrinsic property of the K^d molecule and not due to use of a murine/human chimeric protein. Binding constants arederived for a series of peptides interacting with empty K^d heterodimers. The dissociation constants of four known K^d-restricted peptides range from 2.3 X 10^(-7) to 3.4 X 10^(-8) M. Using a series of 24 analog peptides, the effects of length and peptide composition on binding affinity of one K^d-restricted peptide are explored, and the results are interpreted with reference to the known three dimensional structures of class I MHC protein/peptide complexes.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/bi00192a020DOIArticle
http://pubs.acs.org/doi/abs/10.1021/bi00192a020PublisherArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1994 American Chemical Society. Published in print 1 July 1994. Supported by a research award from the Arthritis Foundation (P.J.B.), the Howard Hughes Medical Institute (M.L.F., J.J., P.J.B.), a Howard Hughes Medical Institute predoctoral fellowship (R.M.R.F.), and an NIH training grant (T32-CA09255 to T.J.T.). We thank Dan Vaughn, Tsutomu Arakawa, and Malini Raghavan for helpful discussions, Marcus Chen for making Figure 4, the Caltech Microchemical Facility for N-terminal sequence analyses, and Malini Raghavan for critical reading of the manuscript.
Funders:
Funding AgencyGrant Number
Arthritis FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIH Predoctoral FellowshipT32-CA09255
Issue or Number:26
Record Number:CaltechAUTHORS:20170406-135433740
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170406-135433740
Official Citation:Effects of Peptide Length and Composition on Binding to an Empty Class I MHC Heterodimer Margaret L. Fahnestock, Jennifer L. Johnson, R. M. Renny Feldman, Theodore J. Tsomides, John Mayer, Linda O. Narhi, and Pamela J. Bjorkman Biochemistry 1994 33 (26), 8149-8158 DOI: 10.1021/bi00192a020
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75810
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:06 Apr 2017 21:55
Last Modified:03 Oct 2019 16:54

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