A splice variant of HLA-A with a deletion of exon 3 expressed as nonmature cell-surface glycoproteins forms a heterodimeric structure with full-length HLA-A.

Alternatively spliced isoforms of the major histocompatibility complex (MHC) class I genes have been reported in many different species and therefore alternative splicing has been observed to be an additional layer of diversity in the MHC class I region. Here we show the characterization of a HLA-A splice variant in the human peripheral blood mononuclear cells (named "HLA-AΔE3"). This transcript is characterized by the deletion of exon 3 that encodes the α2 domain of the full-length HLA-A protein. Cell surface biotinylation experiments indicated that HLA-AΔE3 is able to be transported to the cell surface, as a 34-KDa glycoprotein that is totally sensitive to endoglycosidase-H treatment. Under nonreducing conditions, HLA-AΔE3 can form disulfide-linked homodimers on the cell surface. Furthermore, co-immunoprecipitation studies revealed that HLA-AΔE3 could interact with full-length HLA-A, forming a heterodimeric complex. These findings suggest that the splice variants of HLA-A under steady-state conditions may have an important function in regulating immune homeostasis.