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Published July 1, 1994 | metadata_only
Journal Article

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


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.

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.

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August 20, 2023
August 20, 2023