MHC class I ligands

Figure 7.7. Molecular structures of three potential MHC class I ligands consisting of poly-N-acylaled pep-tidic amines (PAA).

The rules for peptide selection by MHC class I molecules were defined by the characterization of peptide mixtures extracted from class I complexes [33], and furthermore, by the effects of collections of different peptides on binding to MHC molecules and by the response of cytotoxic T cells on these presented peptides [34]. Crystal structure analyses of defined MHC-peptide and MHC-peptide-T-cell receptor (TCR) complexes [35-38] gave detailed information on the molecular interaction between peptides and MHC proteins. MHC class I ligands are mainly octa- or nonapeptides and obey allele-specific sequence motifs carrying prominent anchor residues [24], The peptide-binding groove offers specific pockets to interact with these anchor residues [35]. 

Tormo, J., Natarajan, K., Margulies, D. H., and Mariuzza, R. A. (1999). Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. Nature 402, 623-631. 

Peptides that serve as ligands for major histocompatibility complex (MHC) class I molecules can activate vomeronasal sensory neurons. These peptides contain nine amino acid residues and activate sensory neurons from the V2 receptor... 

Fig. 5. Platform sequence alignments of the MHC class I-like ligands of NKG2D. Sequences of MIC-A and -B, the ULBPs and the RAE-ls have been aligned, divided by family and domain, using CLUSTALW (Thompson et al, 1994). Note that the alignments across families are only very approximate at these levels of sequence identity. Sequences have been numbered from the initiator methionine in the leader peptide, but only the residues in the mature proteins have been shown. Cysteines have been highlighted, and disulhde bond partners have been indicated with matching symbols (, f). For the MIC sequences, allelic substitutions have been indicated by the additional residues shown below the sequences (deletions are indicated with an X ). Diamonds below the sequences indicate NKC2D contact positions, based on the known complex structures (MIC-A 001, ULBPS, and RAE-1/5).

A prerequisite for CTL-mediated immune response is the formation of the MHC-class I-peptide complex and subsequent recognition by the T-cell repertoire, which can be analyzed in cell lysis assays with MCr-loaded target cells. Chromium release is a measure for peptide-induced cell lysis by CTL, and indicates the potency of the peptide to serve as an allele-specific epitope. A synthetic epitope has been identified with the peptide library approach to elucidate the molecular basis for the observed cross-recognition of two ligands by a single receptor [53]. 

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