Distinct regulation of HLA class II and class I cell surface expression inthe THP-1 macrophage cell line after bacterial phagocytosis

Expression of HLA and CD1b molecules was investigated in the THP-1 macropha ge cell line within 2 weeks following phagocytosis of mycobacteria or Esche richia coli. During the first 2-3 days, cell surface expression of HLA clas s II and CD1b was drastically downmodulated, whereas HLA class I expression was up-modulated. In the following days both HLA class II and CD1b express ion first returned to normal, then increased and finally returned to normal with kinetics similar to that observed for the steadily increased HLA clas s I. The initial down-modulation of HLA class II and CD1b cell surface anti gens was absolutely dependent on phagocytosis of bacteria. Further studies indicated that initial HLA class II cell surface down-modulation (1) was no t due to reduced transcription or biosynthesis of mature HLA class II heter odimers, (2) was only partially, if at all, rescued by treatment with IFN-g amma, although both mRNA and corresponding intracellular proteins increased up to sixfold with respect to untreated cells, and (3) resulted in failure of THP-I cells to process and present mycobacterial antigens to HLA-DR-res tricted antigen-specific T cell lines. The existence of a transient block o f transport of mature HLA class ii heterodimers to the cell surface in the first days after phagocytosis of bacteria may have negative and positive co nsequences: it decreases APC function early but it may increase it later by favoring optimal loading of bacterial antigens in cellular compartments at high concentration of antigen-presenting molecules.