Abstract
Class I major histocompatibility complex (MHC) molecules bind peptides derived from degraded proteins for display to T cells of the immune system. Peptides bind to MHC proteins with varying affinities, depending upon their sequence and length. We demonstrate that the thermal stability of the MHC-peptide complex depends directly on peptide binding affinity. We use this correlation to develop a convenient method to determine peptide dissociation constants by measuring MHC-peptide complex stability using thermal denaturation profiles monitored by circular dichroism.
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Selected References
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- Bjorkman P. J., Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59:253–288. doi: 10.1146/annurev.bi.59.070190.001345. [DOI] [PubMed] [Google Scholar]
- Bouvier M., Wiley D. C. Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules. Science. 1994 Jul 15;265(5170):398–402. doi: 10.1126/science.8023162. [DOI] [PubMed] [Google Scholar]
- Fahnestock M. L., Johnson J. L., Feldman R. M., Neveu J. M., Lane W. S., Bjorkman P. J. The MHC class I homolog encoded by human cytomegalovirus binds endogenous peptides. Immunity. 1995 Nov;3(5):583–590. doi: 10.1016/1074-7613(95)90129-9. [DOI] [PubMed] [Google Scholar]
- Fahnestock M. L., Johnson J. L., Feldman R. M., Tsomides T. J., Mayer J., Narhi L. O., Bjorkman P. J. Effects of peptide length and composition on binding to an empty class I MHC heterodimer. Biochemistry. 1994 Jul 5;33(26):8149–8158. doi: 10.1021/bi00192a020. [DOI] [PubMed] [Google Scholar]
- Fahnestock M. L., Tamir I., Narhi L., Bjorkman P. J. Thermal stability comparison of purified empty and peptide-filled forms of a class I MHC molecule. Science. 1992 Dec 4;258(5088):1658–1662. doi: 10.1126/science.1360705. [DOI] [PubMed] [Google Scholar]
- Fremont D. H., Matsumura M., Stura E. A., Peterson P. A., Wilson I. A. Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science. 1992 Aug 14;257(5072):919–927. doi: 10.1126/science.1323877. [DOI] [PubMed] [Google Scholar]
- Ljunggren H. G., Stam N. J., Ohlén C., Neefjes J. J., Höglund P., Heemels M. T., Bastin J., Schumacher T. N., Townsend A., Kärre K. Empty MHC class I molecules come out in the cold. Nature. 1990 Aug 2;346(6283):476–480. doi: 10.1038/346476a0. [DOI] [PubMed] [Google Scholar]
- Parham P., Androlewicz M. J., Holmes N. J., Rothenberg B. E. Arginine 45 is a major part of the antigenic determinant of human beta 2-microglobulin recognized by mouse monoclonal antibody BBM.1. J Biol Chem. 1983 May 25;258(10):6179–6186. [PubMed] [Google Scholar]
- Parker K. C., DiBrino M., Hull L., Coligan J. E. The beta 2-microglobulin dissociation rate is an accurate measure of the stability of MHC class I heterotrimers and depends on which peptide is bound. J Immunol. 1992 Sep 15;149(6):1896–1904. [PubMed] [Google Scholar]
- Schumacher T. N., Heemels M. T., Neefjes J. J., Kast W. M., Melief C. J., Ploegh H. L. Direct binding of peptide to empty MHC class I molecules on intact cells and in vitro. Cell. 1990 Aug 10;62(3):563–567. doi: 10.1016/0092-8674(90)90020-f. [DOI] [PubMed] [Google Scholar]
- Townsend A., Elliott T., Cerundolo V., Foster L., Barber B., Tse A. Assembly of MHC class I molecules analyzed in vitro. Cell. 1990 Jul 27;62(2):285–295. doi: 10.1016/0092-8674(90)90366-m. [DOI] [PubMed] [Google Scholar]