MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I-SPECIFIC AND CLASS-I-RESTRICTED KILLING OF BETA(2)-MICROGLOBULIN-DEFICIENT CELLS BY CD8+ CYTOTOXIC LYMPHOCYTES-T

Cytotoxic T lymphocytes (CTLs) recognize major histocompatibility complex (MHC) class I molecules, normally composed of a heavy chain, a beta2-microglobulin (beta2m), and peptide antigens. Beta2m is considered essential for the assembly and intracellular transport of MHC class I molecules as well as their peptide presentation to CTLs. Contrary to this dogma, we now report the generation of allospecific and restricted CD8+ and TCRalphabeta+ CTLs (where TCR is T-cell receptor) capable of killing beta2m-deficient cells. Such CTLs were obtained by priming mice with live allogeneic beta2m- spleen cells or mutant lymphoma cells producing MHC class I protein but no detectable beta2m. Although both beta2m- and beta2m-expressing lymphoma cells were rejected in allogeneic mice, only the former were efficient inducers of CTLs recognizing beta2m- cells. These CTLs were MHC class I (H-2K(b) or D(b))-specific and CD8-dependent and did not require serum as a source of external beta2m in the culture. They could be induced across major and minor histocompatibility barriers. The H-2-restricted CTLs generated in the latter case failed to kill the antigen-processing-deficient target RMA-S cells. The results show that MHC class I heavy chains in beta2m- cells can be transported to the cell surface and act as antigens or antigen-presenting molecules to allospecific and MHC-restricted CTLs.