Sequence of class II major histocompatibility complex genes from MRL mice. Conserved amino acids in the I-E beta...

Class II major histocompatibility complex molecules are critical in both normal and abnormal immune responses. Both in mice and in humans, these molecules have been implicated in the development of various diseases, including insulin-dependent diabetes mellitus and systemic lupus erythematosus. The MRL/lpr mouse strain spontaneously develops a lupus-like illness with features that include anti-DNA antibodies, glomerulonephritis, and early death. We evaluated the structure of class II molecules from these mice, to investigate for unique sequences that might contribute to autoimmunity. Utilizing the polymerase chain reaction, we sequenced the second exons from the I-A and I-E genes of MRL/lpr and MRL-+/+ mice. We found that at the nucleotide level, there are several changes between MRL class II genes and the previously sequenced "k" haplotype, but at the protein level, they are identical. Furthermore, by comparing the sequences of class II genes from several strains of autoimmune mice, we found that there are conserved amino acids in the third hypervariable region of the I-E beta chain which may be important in the development of autoimmunity.