DPB1 T-cell epitopes: Molecular definition

Abstract

Aim Molecular characterisation of known differences of T-cell recognition of DPB1 alleles. Methods Propositional logic algorithm to search for best sequence properties to account for reported T-cell recognition differences. Results DPB1*09:01:01, DPB1*10:01 and DPB1*17:01 have been reported by Fleischhauer et al. to be mismatch high-risk (group 1) and DPB1*03:01:01, DPB1*14:01:01 and DPB1*45:01 to be mismatch intermediate-risk (group 2). DPB1 alleles have been previously classified in 4 serologic groups based on 2 dimorphic epitopes, the first epitope defined by amino acid position 56 and the second epitope by positions 85, 86 and 87. Fleischhauer’s group 1 and group 2 DPB1 alleles are both included in serologic group DP3 characterised by 56(E) on one hand and 85(E)-86(A)-87(V) on the other. [Human Immunology 2009 70:836] DP3 alleles can be further classified by amino acid positions 11, 65 and 76 into 3 subgroups that match Fleischhauer’s mismatch high-risk groups. This molecular characterisation into subgroup must be interpreted in the light of higher level groups defined by the 56 and 85–86–87 two dimorphic serologic epitopes. In this context, within the DP3 serologic group, T-cell group 1 is characterised by 11(L)-65(I) with tolerance for variation at position 76. T-cell group 2 is characterised by 65(L)-76(V) with tolerance for variation at position 11. Conclusions If the molecular characterisation of DPB1 T-cell epitopes presented here is correct, then DPB1*35:01:01 and the DPB1*17:01 exon 3 variant DPB1*131:01 should also be included in the high-risk group 1 together with DPB1*09:01:01, DPB1*10:01 and DPB1*17:01. DPB1*104:01 and the DPB1*03:01:01 exon 3 variant DRB1*124:01 should be included in group 2 together with DPB1*03:01:01, DPB1*14:01:01 and DPB1*45:01. DPB1*57:01 might also belong in group 2 depending on the tolerance for variation at position 11 in this group. (All these alleles are known common alleles. Undocumented alleles are excluded.)