Truncation of the A alpha chain of MHC class II molecules results in inefficient antigen presentation to antigen-specific T cells.
Antigen presenting cells (APC) expressing MHC class II molecules composed of chains with part or all of the cytoplasmic domains deleted are inefficient at presenting hen egg lysozyme peptides to antigen specific T cell hybrids compared with APC that express wild-type MHC class II molecules. This effect is most apparent for mutants in which the alpha chain has been truncated. The inefficiency in antigen presentation can be amplified by pulsing the APC for 4 h with peptide rather than having peptide present throughout the presentation assay. Fixation of antigen-pulsed APC improves the capacity of APC with truncated class II molecules to stimulate T cell hybrids. Fixation of APC prior to exposure to antigen also leads to significant improvement in antigen presentation by the truncated class II molecules. Because the inefficiency of a given hybrid for antigen presentation does not correlate with its ability to transduce a signal as measured by protein kinase C translocation, we suggest that defects in this pathway are not the only cause of impaired antigen presentation. However, because previous studies have demonstrated the need for an intact cytoskeleton for successful antigen presentation, we propose that the carboxy truncated class II molecules are inefficient in antigen presentation because they are unable to generate the signal that ultimately leads to their interaction with the cytoskeleton. These observations underscore the complexity of the events that are required for achieving effective interactions between MHC class II molecules and TCR, and suggest, with regard to efficient antigen presentation, that the physical state of the class II molecules is at least as important as their signal transducing capacity.
Wade
W F
WF
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Ward
E D
ED
Rosloniec
E F
EF
Barisas
B G
BG
Freed
J H
JH
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000502:physiology*; D004527:Egg Proteins / Q000276:immunology; D005404:Fixatives / Q000494:pharmacology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000235:genetics; D006825:Hybridomas / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D009113:Muramidase / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D004527:Egg Proteins; D005404:Fixatives; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D009113:Muramidase