ALTERNATIVELY SPLICED MHC CLASS-I MESSENGER-RNAS SHOW SPECIFIC DELETION OF SEQUENCES ENCODING THE EXTRACELLULAR POLYMORPHIC DOMAINS

Analysis of structural diversity at the 5' end of H-2 class I mRNAs showed that a small fraction of K(d) MRNA from L1210 lymphoma (approximately 10%) or from various normal tissue (2 - 3%) of DBA/2 mice carries a precise deletion of the sequences encoding the second extracellular domain. Nucleotide sequence of the coding region of the second domain-lacking K(d) mRNA was found to be identical to the known sequence of the K(d) gene from DBA/2 liver with the exception of the above deletion and a single nucleotide silent substitution at position 150, suggesting that the novel K(d) RNA is a product of the functional K(d) gene. In addition, various normal tissues that are known to express varying levels of K(d) antigen did not show changes in the expression levels of the second domain-lacking K(d) mRNA thus ruling out the possibility that synthesis of this RNA is coupled to control the expression levels of the canonical K(d) mRNA, hence the K(d) antigen. Analysis by polymerase chain reaction showed that all normal tissues including the testis and sperm express this RNA. Preliminary analysis of the K(b) mRNA from the spleen and thymus of C57BL/6 mouse also showed the presence of second domain-lacking K(b) mRNA in these mice. Furthermore, preliminary structural analysis of the D(d) and L(d) mRNAs has revealed additional polymorphic extracellular domain-lacking mRNA species including a first domain-lacking D(d) mRNA and two L(d) mRNAs that lack sequences encoding either the first extracellular domain or the second extracellular domain respectively. These results together show that H-2 mRNAs lacking sequences that specify individual extracellular polymorphic domains are a frequent feature of the structural diversity at the 5' ends of these mRNAs. Potential significance of these domain-lacking H-2 mRNAs is discussed, particularly with regard to the function of the putative encoded peptides as targets of natural killer cells.