The CD8 coreceptor interaction with the α₃ domain of HLA class I is critical to the differentiation of human cytotoxic t-lymphocytes specific for HLA-A2 and HLA-Cw4

The CD8 coreceptor interacts with MHC class I molecules through an acidic loop in the MHC α₃ domain. Mutations in this region reduced binding between cells expressing mutant HLA molecules and CHO cells transfected with CD8 α chain, with mutations at residue 227 having the greatest effects. This study was undertaken to examine the role of the CD8-HLA interaction in the generation of primary and long-term CTLs. HLA-A^*0201 genes (wild type or mutated at residue 227) were transfected into a cell line that lacked expression of HLA-A or B molecules but expressed HLA-Cw4. These cells were used as stimulators for PBLs from a normal donor. Cultures were tested for cytotoxicity at various times thereafter. Transfectants expressing the HLA-A^*0201 mutant gene were poor stimulators of primary HLA-A2-specific CTLs. In long-term culture, HLA-Cw4-specific CTLs predominated, indicating that continuous expansion of allogeneic CTLs depends upon an efficient CD8-MHC class I interaction.