Fig. 2. Human antigen processing mutant cell lines: the derivation of T2 from 731.174.

721.174 (.174) and T2 are two cell line that focused attention on the MHC-II region of the MHC as a place where genes regulating peptide binding by MHC-I and MHC-II were localized. These were eventually identified as the TAP1 and TAP2 genes for MHC-I and HLA-DMA and HLA-DMB genes for MHC-II. The lines within the individual cells represent the two MHC regions present in each cell. T2 arose from an initial somatic cell fusion between .174 (top left) and the T cell line CCRF-CEM (CEM) (top right). .174 has a complete deletion of the HLA complex on one copy of chromosome 6 and a deletion of the MHC-II region of the HLA complex on the other. It expresses no MHC-II on the cell surface because the coding genes are absent but, although the genes encoding HLA-A2 and -B5 are present, A2 surface expression is lower while B5 expression is dramatically reduced it is minimally expressed at the cell surface. CEM has two intact copies of the HLA complex, but MHC-I expression is very low and MHC-II expression is absent for transcriptional reasons. The initial fusion gave rise to a cell line called T1, where one of the CEM copies of chromosome 6 is missing, but it expresses high levels of HLA-A2 and -B5 encoded by .174 because the TAP genes were introduced from the parental CEM line. HLA-DR7 (orange), encoded but not synthesized by CEM, is also highly expressed, presumably because a transcriptional factor(s) derived from .174 has been introduced. The critical genes for MHC-I function encode the TAP1 and TAP2 (dark blue in the figure). T2 resulted from selection for loss of DR7 expression, which eliminated the remaining CEM-derived chromosome 6 and restored the surface expression phenotype of .174.