Overlapping palindromic sequences associated with somatic deletion and meiotic recombination of MHC class I genes

Abstract

H-2L-null variants were immunoselected from a transfected murine fibroblast cell line carrying a single copy H-2L gene, and were characterized to determine the basis for the loss of this MHC class I cell surface product. Molecular analysis indicated that inactivation of H-2L expression in nearly every null clone resulted from an apparent deletion or rearrangement of 5'-flanking and 5'-coding H-2L sequences, with breakpoints consistently mapping to within a 550 bp GC-rich region between exon 1 and the middle of intron 2. Notably, this region of the H-2L gene contains a large number of overlapping, inverted repeat sequences as well as potential topoisomerase I cleavage sites. Examination of several in vivo mutant class I genes, believed to have been generated by recombination, has revealed that each of these genes bears similar palindromic structures overlapping or adjacent to the regions of sequence exchange. These findings suggest that inverted repeat sequences may play a role in recombination and deletion within the MHC class I multigene family.