The mechanisms of peptide exchange and beta 2-microglobulin exchange on cell surface Ld and Kb molecules are noncooperative.
It has previously been shown that the presence of exogenous beta 2-microglobulin (beta 2m) can dramatically enhance the binding of exogenous peptide to cell surface class I MHC. However, the mechanism by which this enhancement takes place is unknown. Two models have been proposed to explain this phenomenon. In the first model, the exchange of peptide and the exchange of beta 2m are cooperative processes. In the alternative model, beta 2m stabilizes free class I heavy chains to increase the total number of peptide binding sites available. In this report, we have examined the relationship between peptide exchange and beta 2m exchange. Comparisons of Ld and Kb complexes formed with peptides possessing widely disparate affinities revealed a reciprocal correlation between the peptide off-rate and the rate of beta 2m exchange. This result indicates that peptide exchange and beta 2m exchange are noncooperative processes that may, in fact, antagonize one another. These findings provide the first demonstration of peptide-specific influences on the rate of beta 2m exchange and suggest that exogenous beta 2m promotes peptide binding by maintaining class I heavy chains in a peptide-receptive state.
Cook
J R
JR
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Myers
N B
NB
Hansen
T H
TH
D000818:Animals; D002455:Cell Division / Q000276:immunology; D006183:H-2 Antigens / Q000187:drug effects / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D007739:L Cells; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D001613:beta 2-Microglobulin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D008565:Membrane Proteins; D010455:Peptides; D001613:beta 2-Microglobulin