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

Abstract

Listen

Translate article

Nucleotide sequence analysis of mRNA from the H-2K locus of the CBA.M523 mouse, which has the class I murine MHC mutation H-2K kml, has established the only alteration to be at the codon for amino acid position 152 as compared to the sequence of standard K k 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 K k sequence, changing Asp (GAT) in K k to Ala (GCT) in K kml. The GCT codon occurring in K kml may be the result of a gene conversion event because a potential donor gene, the pH-2III pseudogene of H-2 k, is transcribed in the CBA.M523 mouse and has a GCT codon at amino acid position 152. This sequence information obtained for K kml also demonstrates that K k 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.