Amino acid comparison of the class I antigens of mouse major histocompatibility complex

Abstract

The amino acid sequences of the mouse class I antigens are shown. Residues which are conserved between all clas~ I molecules are specified only on the H-2K d reference sequence at the top of each page, and are left as blank spaces elsewhere. The amino acid sequences of the characterized class I mutants are shown only in those domains bearing amino acid substitutions with respect to their parental alleles. Dashes are used to indicate the absence of codon(s) in certain genes relative to the others to facilitate sequence alignment. Sequences are listed from N-to C-termini starting with the c~l domain. Macintosh discs containing the sequences will be provided upon request.

Design of Agonistic Altered Peptides for the Robust Induction of CTL Directed towards H-2Db in Complex with the Melanoma-Associated Epitope gp100

“…The p2Gp3P modifications in EGP establish novel essential interactions within the binding cleft of H-2D b , mainly between p3P and heavy chain residue Y159, conserved among most known MHC-I sequences across species (13). In conclusion, this study suggests an alternative approach for the design of optimal peptide mimotopes that overcome self-tolerance and could be used as target antigens for immunotherapy of cancer.…”

“…However, comparative structural analysis indicated subtle but important differences at positions 2 and 3 as a structural basis for the higher affinity and stability of EGP when compared with KVP and EGS. A hydrogen bond interaction is formed in all three structures between the hydroxyl group of Y159, conserved among most known MHC-I molecules (13), and the oxygen atom of peptide residue p1, resulting in a precise orientation of the side chain of Y159 (Fig. 4B).…”

Vesicular stomatitis virus antigenic octapeptide N52-59 is anchored into the groove of the H-2Kb molecule by the side chains of three amino acids and the main-chain atoms of the amino terminus.

“…In contrast, at the C terminus the side chain of Leu-8 seems directly involved in binding to Kb because the interaction of peptide analogs that have an Ala-8 (Leu-*Ala replacement) or complete deletion of residue 8 seems to be affected to a similar extent. Because the subsites at both ends of the MHC antigen binding groove are highly conserved among most class I molecules (17,18), it is likely that, in general, these sites are involved in binding the N and C termini of peptides.…”

“…The antigen binding groove has subsites in the form of pockets, several of which are occupied by electron-dense material in the x-ray crystal structure of all three HLA molecules studied (12,15,16). Interestingly, most of the polymorphic residues that distinguish MHC class I allelic products map to residues lining the cleft, some of which also impinge into the pockets (17,18). Thus, the chemical and spatial architecture of the groove dictates the structural requirements for the peptides that can occupy the cleft of the MHC molecules.…”

Transmembrane domain length variation in the evolution of major histocompatibility complex class I genes.

“…To understand the evolution of MHC class I loci, we have initially focused upon the transmembrane domain (TM)-encoding exon (exon 5). This region exhibits relatively low allelic polymorphism and the sequence of the TM is distinctive of various class I subtypes in H-2 and HLA systems (5,6,(18)(19)(20)(21)(22) …”