Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules

Modification of the HER2NEU‐derived tumor antigen GP2 improves induction of GP2‐reactive cytotoxic T lymphocytes

“…10,11 Peptides were purchased from Genemed Synthesis Inc., (San Francisco, CA). Synthesis was carried out by a standard solid-phase method based on fluorenylmethoxycarbonyl chemistry.…”

“…10,11 Many identified tumor-associated antigens including GP2, however, lack at least 1 of these major anchor residues. 12,13 This means that these tumor antigens bind poorly to HLA-A*0201 and only a limited number of antigen-MHC complexes are expressed on the cell surface.…”

Efficient binding to the MHC class I Kd molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif

“…Crystallographic studies of the MHC molecules in complex with peptides [2,3], chemical analyses of mixtures of naturally occurring peptides bound to MHC alleles [4] and binding tests performed either with individual synthetic peptides [5,6] or with peptide libraries [7] revealed biochemical details of MHC-peptide interactions. These studies identified allele-specific motifs containing critical or 'anchor' residues at defined positions within the sequences of peptides that bind to each particular allele.…”

A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection

“…However, it was also noted that a significant proportion of binders do not strictly conform to canonical motifs, and were therefore missed. To overcome this limitation, the present analysis uses a very broad A*0201 motif previously characterized by our laboratory (44,52), which identifies peptides with L, I, V, M, A, T, or Q in position 2 and L, I, V, M, A, and T at the C terminus. This motif is present in 21 of 22 (95%) well-characterized EBV-, HIV-, influenza-, and tumor Ag-derived A*0201-restricted epitopes independently reported in the literature (see Supplemental Table IB).…”