DISTRIBUTION OF HLA-G ALTERNATIVE MESSENGER-RNAS INCLUDING SOLUBLE FORMS IN NORMAL LYMPHOCYTES AND IN LYMPHOID CELL-DERIVED LEUKEMIA

The non-classical HLA-G gene is the only class I antigen expressed in trophoblasts at the maternofetal interface. In placenta, the HLA-G gen e produces several alternatively spliced isoforms encoding bound-membr ane proteins (G1, G2, G3 and G4) lacking, respectively, exon 7; exons 7 and 3; exons 7, 3 and 4, and exons 7 and 4. In addition, two isoform s (Gls and G2s) containing an intron 4 sequence are able to encode sol uble antigens. We have recently reported that the HLA-G gene is transc riptionally active in lymphocytes and is not transcribed in CD34+ cell s, polynuclear cells or monocytes. To investigate the functional signi ficance of the different isoforms in lymphocytes, we studied their dis tribution in normal T and B lymphocytes and in malignant lymphoid cell s by using the RT-PCR technique followed by hybridization with exon-sp ecific probes and sequencing assays. In transcriptionally active lymph ocytes, the HLA-G primary transcript is the major form and is differen tially spliced in B and T lymphocytes: (i) Gls is found in several sam ples of T and B cells whereas G2s is only transcribed in T lymphocytes , (ii) the G4 isoform is never detected in B lymphocytes. In addition, we have shown that HLA-G is inactive in some samples of lymphocytes. Our data suggest that HLA-G transcription is regulated at the initiati on level and at the subsequent splicing. These two levels of regulatio n may be dysregulated in some cases of T-ALL and CLL. The potential fu nctions of the HLA-G alternative forms in lymphocytes, such as peptide binding and modulation of the immune response, are discussed.