Gene conversion between murine class II major histocompatibility complex loci. Functional and molecular evidence from the bm 12 mutant.

Open Access
Publisher Website
Google Scholar
Abstract
The experiments presented define the molecular basis of the [mouse] bm12 mutation. Initial characterization of an alloreactive T cell clone, 4.1.4, showed this clone to recognize an allodeterminant present on the E.beta.b and A.beta.bm12 chains, but not on the bm12 parent A.beta.b chain. To define the extent of sequence shared between the I-E.beta. product and the mutant I-A.beta. product, a cDNA [complementary DNA] clone of the E.beta.b gene was isolated and its nucleotide sequence was determined. Comparison of the nucleotide sequences of E.beta.b, A.beta.b, and A.beta.bm12 shows the A.beta.bm12 gene to be identical to the E.beta.b gene in the region where it differs from its A.beta.b parent. The bm12 mutation may have arose by gene conversion of this region, which spans 14 nucleotides between amino acid residues 67-71 of the mature A.beta. chain, from the E.beta.b locus to the corresponding position at the A.beta.b locus. Recognition of this region, which spans one of the previously defined E.beta. allelic "hypervariable" regions, by an alloreactive T cell clone provides the 1st direct evidence of the functional importance of these hypervariable regions in T cell stimulation. The identification of a gene converson event involving one of these allelic variable regions implicates conversion as a mechanism that acts on class II .beta. genes to create sequence diversity in regions of Ia molecules; these molecules interact with foreign antigen or a T cell receptor, regions where protein sequence polymorphism would presumbly be selected for by the expanded ability it affords the orgainsm to mount effective immune responses against a wider variety of foreign antigens.