A novel variant of DR4 (DRB10421) identified in a patient with polychondritis

Class II major histocompatibility complex (MHC) molecules bind peptides and present them to helper T lymphocytes as the initial step of an immune response. The specificity of peptide binding by class II molecules is determined by aminoacid exchanges in the hypervariable regions. There are groups of HLA-DRB1 gene alleles, which differ from each other by only one or two aminoacids, while the members of one group may differ from members of another group by as many as 10-15 aminoacid exchanges. The largest such group is DRB1*04, of which there are at present 20 different alleles known (Bodmer et al. 1994; J. McCluskey, personal communication). In the process of HLA-DRB1*04 subtyping of patients with polychondritis, which is associated with DR4, we identified one patient (SMH), whose DNA displayed a novel pattern of oligonucleotide reactivity. The oligonucleotide typing results suggested one or more nucleotide differences in the region encoding aminoacid 37 of the DRB1*0401 allele.