title: Analysis of major histocompatibility complex class I folding: novel insights into intermediate forms.
abstract: Folding around a peptide ligand is integral to the antigen presentation function of major histocompatibility complex (MHC) class I molecules. Several lines of evidence indicate that the broadly cross-reactive 34-1-2 antibody is sensitive to folding of the MHC class I peptide-binding groove. Here, we show that peptide-loading complex proteins associated with the murine MHC class I molecule K(d)  are found primarily in association with the 34-1-2(+)  form. This led us to hypothesize that the 34-1-2 antibody may recognize intermediately, as well as fully, folded MHC class I molecules. To further characterize the form(s) of MHC class I molecules recognized by 34-1-2, we took advantage of its cross-reactivity with L(d) . Recognition of the open and folded forms of L(d)  by the 64-3-7 and 30-5-7 antibodies, respectively, has been extensively characterized, providing us with parameters against which to compare 34-1-2 reactivity. We found that the 34-1-2(+) L(d)  molecules displayed characteristics indicative of incomplete folding, including increased tapasin association, endoplasmic reticulum retention, and instability at the cell surface. Moreover, we show that an L(d) -specific peptide induced folding of the 34-1-2(+) L(d)  intermediate. Altogether, these results yield novel insights into the nature of MHC class I molecules recognized by the 34-1-2 antibody.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Simone
authors.forename: A
authors.initials: A
authors.lastname: Tuli
authors.forename: P D
authors.initials: PD
authors.lastname: Simone
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: J C
authors.initials: JC
authors.lastname: Solheim
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D018360:Crystallography, X-Ray; D005434:Flow Cytometry; D006031:Glycosylation; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000502:physiology; D017510:Protein Folding; D055550:Protein Stability
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin