EFFECTS OF PEPTIDE LENGTH AND COMPOSITION ON BINDING TO AN EMPTY CLASS-I MHC HETERODIMER

被引:45
作者
FAHNESTOCK, ML
JOHNSON, JL
FELDMAN, RMR
TSOMIDES, TJ
MAYER, J
NARHI, LO
BJORKMAN, PJ
机构
[1] CALTECH,DIV BIOL 15629,PASADENA,CA 91125
[2] CALTECH,HOWARD HUGHES MED INST,PASADENA,CA 91125
[3] MIT,CTR CANC RES,CAMBRIDGE,MA 02139
[4] MIT,DEPT BIOL,CAMBRIDGE,MA 02139
[5] AMGEN BOULDER INC,BOULDER,CO 80301
[6] AMGEN INC,THOUSAND OAKS,CA 91320
关键词
D O I
10.1021/bi00192a020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, 1658-1662]. 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 Kd heterodimer. The majority of empty heterodimers are stable at 37 degrees 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 are derived 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.
引用
收藏
页码:8149 / 8158
页数:10
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