EXPRESSION OF BETA(2)-MICROGLOBULIN-FREE HLA CLASS-I ALPHA-CHAINS ON ACTIVATED T-CELLS REQUIRES INTERNALIZATION OF HLA CLASS-I HETERODIMERS

HLA class I molecules on activated T cells are expressed as heterodime rs associated with beta(2)-microglobulin (beta(2)-m) and also beta(2)- m-free HLA class I alpha-chains. Mechanisms leading to the expression of the activation associated beta(2)-m-free HLA class I alpha-chains a re poorly defined, however. Upon enzymatical removal of HLA class I al pha-chains on activated T cells, re-expression is observed within minu tes upon reculture, reaching half-maximal levels within 1 hr. This pro cess is independent of de novo protein synthesis and of export of newl y synthesized proteins. Inhibition of the formation of coated pits by potassium depletion of cells abrogated the re-expression of HLA class I alpha-chains, suggesting that recycling events of HLA class I hetero dimers via endosomal compartments are required for the generation of m onoclonal antibody LA45-reactive a-chains. Furthermore, the rate of al pha-chain generation seems to be governed by the amount of cell surfac e-expressed HLA class I heterodimers. Taken together these findings su ggest that beta(2)-m-free HLA class I alpha-chains are generated durin g the process of class I heterodimer recycling.