Definition of peptide binding motifs amongst the HLA‐A*30 allelic group

Abstract

HLA class I molecules present endogenously processed peptide ligands for surveillance by the T-cell receptor. This potentially immunogenic surface of HLA and peptide is a consequence of the polymorphism found within the HLA molecule and its preference for ligand binding together with peptide conformation within the binding groove. To investigate the relation between the polymorphic differences between some closely related HLA alleles and their effect on peptide preference, transfectants were established, each containing one of four allelic variants of HLA-A*30. Peptides from all four transfectants were eluted, and both individual ligands and peptide pools were sequenced. The data shows two distinct peptide motifs which distinguish A*3001 from the other three known A*30 variants. Differences in preferences at minor positions within the peptide sequence were noted between A*3002, A*3003 and A*3004, providing additional evidence of the implications of sequence polymorphism to HLA function.

Rapid Definition of Five Novel HLA-A∗3002-Restricted Human Immunodeficiency Virus-Specific Cytotoxic T-Lymphocyte Epitopes by Elispot and Intracellular Cytokine Staining Assays

“…A recently undertaken comparison of the peptide binding motifs of A‫1003ء‬ and A‫2003ء‬ reveals distinctive differences between the peptides bound by these two subtypes (18). As previously described for HLA-A2 subtypes (4), these binding differences correspond to functional differences, in keeping with the data above showing that A‫-1003ء‬positive targets pulsed with the A‫-2003ء‬defined epitopes were not recognized by A‫-2003ء‬positive effectors.…”

“…To illustrate this point, the five HLA-A‫2003ء‬ epitope peptides defined above are aligned in Table 1 with the A‫-2003ء‬binding peptides that were sequenced (18). In contrast, there appears to be a greater restriction in the residues that occupy P1 than P2 for the A‫-2003ء‬binding peptides aligned in Table 1, with seven of nine peptides having either Arg or Lys in this position.…”

Motif Inference Reveals Optimal CTL Epitopes Presented by HLA Class I Alleles Highly Prevalent in Southern Africa

“…Table I These data indicate a broad specificity at P2, but with positively and negatively charged residues not tolerated; and a strong preference for Tyr at PC. To examine the motif that would be inferred for HLA-A*2902 based solely on the HLA amino acid sequence, a comparison was made between HLA-A*2902 and the closely related A19 alleles, A*3001, A*3002, A*3003, A*3004, A*3101, and A*3303 (25,26), for which the motifs have also been defined. From these data, one would predict a similarly capacious B pocket characteristically containing large to medium-sized hydrophobic residues at P2 for A*2902, consistent with what is observed for the defined A*2902-restricted epitopes that all have Phe or Tyr at P2 (Table II).…”

Promiscuous CTL Recognition of Viral Epitopes on Multiple Human Leukocyte Antigens: Biological Validation of the Proposed HLA A24 Supertype

“…The biological significance of several HLA supertypes has also been demonstrated, with reports of individual peptides binding to multiple HLA alleles and T cell recognition of such peptides presented by the different class I alleles (10 -17). The HLA-A24-supertype was proposed in 1999 by Sette and Sidney (8) to include A*2301, A*2402, and A*3001 on the basis of similarities between the published peptide binding motifs for A*2402 (18,19) and A*3001 (20) and homology with two peptides known to bind to A*2301 (21,22). The alleles A*2403, A*2404, A*3002, and A*3003 were also tentatively included within the A24 supertype on the basis of possessing identical or conservatively similar amino acid residues surrounding the likely B-and F-pockets in these alleles compared with A*2301, A*2402, and A*3001.…”