TRUNCATION OF THE A(ALPHA) CHAIN OF MHC CLASS-II MOLECULES RESULTS ININEFFICIENT ANTIGEN PRESENTATION TO ANTIGEN-SPECIFIC T-CELLS

Antigen presenting cells (APC) expressing MHC class II molecules compo sed of chains with part or all of the cytoplasmic domains deleted are inefficient at presenting hen egg lysozyme peptides to antigen specifi c T cell hybrids compared with APC that express wild-type MHC class II molecules. This effect is most apparent for mutants in which the alph a chain has been truncated. The inefficiency in antigen presentation c an be amplified by pulsing the APC for 4 h with peptide rather than ha ving peptide present throughout the presentation assay. Fixation of an tigen-pulsed APC improves the capacity of APC with truncated class II molecules to stimulate T cell hybrids. Fixation of APC prior to exposu re to antigen also leads to significant improvement in antigen present ation by the truncated class II molecules. Because the inefficiency of a given hybrid for antigen presentation does not correlate with its a bility to transduce a signal as measured by protein kinase C transloca tion, we suggest that defects in this pathway are not the only cause o f impaired antigen presentation. However, because previous studies hav e demonstrated the need for an intact cytoskeleton for successful anti gen presentation, we propose that the carboxy truncated class II molec ules are inefficient in antigen presentation because they are unable t o 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 molecule s is at least as important as their signal transducing capacity.