Gastric cancer progression may involve a shift in HLA-E profile from an intact heterodimer to β2-microglobulin-free monomer.

Phenotypic expression of human leukocyte antigen (HLA)-E on the surface of tumor lesions includes intact heterodimer [HLA-E heavy chain and β2-microglobulin (β2m)] and β2m-free monomer. Anti-HLA-E monoclonal antibodies (mAbs), MEM-E/02 or 3D12 bind to the peptide sequences in β2m-free HLA-E, which is common and shared with HLA-Ia monomers. A newly developed monospecific anti-HLA-E mAb (TFL-033) recognizes HLA-E-restricted peptide sequences on α1 and α2 helices away from β2-m-site. Tumor progression may involve shedding of β2-m from HLA-E or overexpression of β2m-free monomers. There is a need to identify and distinguish the different phenotypic expression of HLA-E, particularly the intact heterodimer from the β2m-free monomer on the surface of tumor lesions. Because of the unique peptide-binding affinities of the mAbs, it is hypothesized that TFL-033 and MEM-E/02 may distinguish the phenotypic expressions of cell surface HLA-E during stages of tumor progression. Only TFL-033 stained diffusely the cytoplasm of normal mucosa. The incidence and intensity of TFL-033 staining of the cell surface in early stages, poorly or undifferentiated and non-nodal lesions and in diffuse carcinoma is greater than that of MEM-E/02. Whereas MEM-E/02 stained terminal stages, adenocarcinoma and lymph node metastatic lesions intensely, either owing to increased expression of β2m-free HLA-E with tumor progression or owing to expression of HLA-Ia molecules. Our study evaluates the relative diagnostic potential of HLA-E-monospecific TFL-033 and the HLA-Ia-reactive MEM-E/02 for determining the specific distribution and immunodiagnosis of different phenotypic expression HLA-E in tumor lesions, and the structural and functional alterations undergone by HLA-E during tumor progression.