Cutting edge: H-2DM is responsible for the large differences in presentation among peptides selected by I-Ak during antigen processing.
We quantitated the amounts of peptides from hen egg-white lysozyme presented by I-A(k) molecules in APC lines. The large chemical gradient of presentation of the four hen egg-white lysozyme epitopes observed in cell lines expressing HLA-DM or H-2DM (referred to in this study as DM) was significantly diminished in the T2.A(k) line lacking DM. Differences in levels of presentation between wild-type and DM-deficient APC were observed for all four epitopes, but differences were most evident for the highest affinity epitope. As a result of these quantitative differences in display, presentation of all four epitopes to T cells was impaired in the line lacking DM. The binding affinity of the pool of naturally processed peptides from DM-expressing lines was higher than that from the DM-deficient line. Thus, using a direct biochemical approach in APC, we demonstrate that DM influences the selection of peptides bound to MHC class II by favoring high affinity peptides.
Lovitch
Scott B
SB
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Petzold
Shirley J
SJ
Unanue
Emil R
ER
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D006681:HLA-D Antigens / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009113:Muramidase / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*
D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; C421864:hen egg lysozyme; D009113:Muramidase