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Thermolabile H-2K^b Molecules Expressed by Transporter Associated with Antigen Processing-Deficient RMA-S Cells Are Occupied by Low-Affinity Peptides¹

A. Dharshan De Silva^*, Alina Boesteanu^*, Rui Song, Nancy Nagy, Edward Harhaj^*, Clifford V. Harding and Sebastian Joyce^2,*

^* Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033; and Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106

RMA-S cells do not express functional TAP, yet they express MHC class I molecules at the cell surface, especially at reduced temperatures (26°C). It is generally assumed that such class I molecules are "empty," devoid of any associated peptide. A radiochemical approach was used to label class I-associated peptides and to determine the extent to which K^b molecules in RMA-S cells are associated with peptides. These studies revealed that at 26°C K^b molecules in RMA-S cells are occupied with self-peptides. Such peptides stably associate with K^b at 26°C but easily dissociate from them at 37°C, suggesting low-affinity interactions between K^b and the associated peptides. At 26°C, at least some of these K^b molecules are stably expressed in a peptide-receptive state on the cell surface, whereas at 37°C they are short lived and are only transiently capable of binding and presenting exogenously supplied OVA 257–264 peptide for presentation to CD8⁺ K^b-restricted T lymphocytes. Thus contrary to current models of class I assembly in TAP-deficient RMA-S cells, the presumably "empty" molecules are in fact associated with peptides at 26°C. Together, our data support the existence of an alternative mechanism of peptide binding and display by MHC class I molecules in TAP-deficient cells that could explain their ability to present Ag.

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