Major histocompatibility complex encoded class I molecules are integrally involved in the presentation of viral antigens to cytotoxic T lymphocytes (CTL). The goal of these studies is to gain an understanding of the regulation of expression, and the functional and antigenic properties of these molecules. It has shown that multiple class I molecules can be generated from single genes by alternative splicing of pre-mRNAs. Particular alternatively spliced gene products affecting the C-terminus have been shown to distinguish H-2k molecules from H-2D molecules. For H-2K molecules from H-2D molecules. For H-2K molecules, the splicing pattern favoring the use of a long exon 8 could be correlated with a potential lariat branch point adenosine 28 bp upstream of the splice junction. Elimination of this adenosine altered the pattern of pre-mRNA splicing in H-2K molecules resulting in a predominance of short exon 8 encoded sequences. The splicing pattern of H-2D region molecules could not be correlated with this base alone. Previous studies have suggested that MHC class I molecules bind and present peptides to CTL, and that the peptides bind to two alpha helices in the class I molecule consisting of residues 50-84 and 138-180. For the M1 peptide of the influenza virus matrix protein, it was shown that the amino acid substitutions at positions 152 and 156 of HLA-A2.1 in the second alpha helix are important for recognition by influenza virus restricted CTL. However, it was shown that the failure to recognize complexes between the peptide and these mutant HLA-A2.1 molecules was due to T -cell receptor specificity and not the failure of the HLA-A2.1 molecules to bind peptide. For CTL recognition of HLA-A3 class I molecules the nature of the amino acid difference at position 152 was shown to be critical for distinguishing HLA-A3.1 and HLA3.2 molecules either by all-immune CTL or vitally restricted CTL. Different viruses and target cells did not alter this recognition pattern. Thus both of these studies emphasize that the region between residues 150 and 160 of class I molecules as being critical for antigen presentation to cytotoxic T lymphocytes.
