New DQA1 allele specific antibody against epitope 2D (an exon 1 encoded amino acid). Considerations for alleles under the same P-group designation.

The majority of polymorphisms of the Human Leukocyte Antigen (HLA) proteins are clustered at the peptide binding domain (PBD), defined as the area coded by exon 2 and 3 for class I and exon 2 for class II. HLA alleles with the same amino acid (AA) sequence at the PBD are considered functionally equivalent and can be grouped under the same P-group designation. Here we present a case of a kidney recipient, typed as DQA1*01:04, 01:05 and DQB1*05:01P, 05:03, who developed antibodies against all DQ antigens on our Luminex Single Antigen (LSA) panel. Our LSA panel does not include DQA1*01:05 or 01:04, but both alleles belong to the DQA1*01:01P group and beads carrying DQA1*01:01 tested positive. Mature protein sequence alignment demonstrated a single AA mismatch between DQA1*01:04/01:05 and DQA1*01:01 located at position 2 (G vs D), which is encoded by exon 1. Luminex assay by another manufacturer which include a bead carrying patient's own DQA1* type and crossmatch studies with surrogate donors confirmed the presence of an antibody against mismatched epitope 2D. This case illustrates that alleles included in the same P-group may have polymorphisms able to trigger immunological responses and brings attention to the fact that some mature HLA proteins express AA encoded by exon 1, which is structurally part of the PBD.