Open AccessAnalysis of major histocompatibility complex class I folding: novel insights into intermediate forms
Author(s) -
Simone L. C.,
Tuli A.,
Simone P. D.,
Wang X.,
Solheim J. C.
Publication year - 2012
Publication title -
tissue antigens
Language(s) - English
Resource type - Journals
eISSN - 1399-0039
pISSN - 0001-2815
DOI - 10.1111/j.1399-0039.2012.01849.x
Subject(s) - major histocompatibility complex , mhc class i , mhc restriction , antigen presentation , folding (dsp implementation) , peptide , chemistry , biology , antigen processing , antigen , microbiology and biotechnology , biochemistry , immune system , genetics , t cell , electrical engineering , engineering
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.