Table II.
Relative binding affinity of the proinsulin peptides to HLA-DR and DQ molecules.
Peptide | DR3 | DR4 | DRB4 | DQ2 | DQ8 |
---|---|---|---|---|---|
B8-22 | >1 250 | >3 333 | >1 000 | >50 | 1 |
B11-25 | 1 250 | 333 | >1 000 | 15 | 1 |
B14-28 | 1 000 | 2 667 | >1 000 | >50 | 61 |
B17-C1 | >1 250 | >3 333 | >1 000 | >50 | >143 |
B20-C4 | 6 | >3 333 | >1 000 | >50 | >143 |
C10-24 | >1 250 | >3 333 | >1 000 | >50 | >143 |
C13-27 | >1 250 | >3 333 | >1 000 | >50 | >143 |
C16-30 | >1 250 | >3 333 | >1 000 | >50 | >143 |
C19-33 | >1 250 | 1 764 | 141 | 15 | 49 |
C22-A1 | 48 | 3 | >1 000 | >50 | >143 |
C25-A4 | >1 250 | 153 | >1 000 | >50 | >143 |
A1-15 | 106 | >3 333 | >1 000 | 5 | 9 |
Results are expressed as a relative binding ratio obtained by dividing the IC50 of the peptides by that of a reference peptide that binds strongly to the HLA molecule. Lower numbers correspond to a higher binding affinity. Bold: binding ratio below 100 (moderate binding) or below 10 (high binding). Each peptide-HLA combination was evaluated in two independent experiments. Peptides were tested at 10 different concentrations up to a maximal concentration of 100 000 nM. This maximal concentration was used to define the maximal relative binding ratio for each HLA molecule tested. The sequences and mean IC50 values of the reference peptides used were: MT2-16 (AKTIAYDEEARRGLE) for DRB1*03:01 (75 nM), HA306-318 (PKYVKQNTLKLAT) for DRB1*04:01 (30 nM), E2/E7 (AGDLLAIETDKATI) for DRB4*01:01 (63 nM), HCI46-63 (EPRAPWIEQEQGPEYWDQE) for DQ2 (DQA1*05:01/DQB1*02:01; 1400 nM) and DQB45-57 (ADVEVYRAVTPLGPPD) for DQ8 (DQA1*03:01/DQB1*03:02; 730 nM). DR3=DRB1*03:01, DR4=DRB1*04:01, DRB4=DRB4*01:01.