The H-2Kkml mutation: a single nucleotide substitution is responsible for multiple functional differences in a class I MHC molecule

Nucleotide sequence analysis of mRNA from the H-2K locus of the CBA.M523 mouse, which has the class I murine MHC mutation H-2Kkml, has established the only alteration to be at the codon for amino acid position 152 as compared to the sequence of standard Kk from both the AKR and CBA inbred mouse lines. Complete sequence information for the nucleotides coding for amino acids 1-292, which includes all of the extracellular protein domains, demonstrated an A---C alteration in the codon for amino acid 152 as compared to the standard Kk sequence, changing Asp (GAT) in Kkml. The GCT codon occurring in Kkml may be the result of a gene conversion in Kkml. The GCT codon occurring in Kkml may be the result of a gene conversion event because a potential donor gene, the pH-2III pseudogene of H-2k, is transcribed in the CBA.M523 mouse and has a GCT codon at amino acid position 152. This sequence information obtained for Kkml also demonstrates that Kk gene transcripts from two genetically distinct inbred mouse lines, CBA and AKR, are completely identical. Finally, several other murine and human class I MHC variants have similar alterations at amino acid position 152 which result in altered biological functions. This information suggests that amino acid 152 is an important part of a T-cell-recognized antigenic determinant on MHC class I antigens.