PMID- 8805247 OWN - NLM STAT- MEDLINE DCOM- 19970218 LR - 20201215 IS - 0960-9822 (Print) IS - 0960-9822 (Linking) VI - 6 IP - 3 DP - 1996 Mar 1 TI - Nonclassical HLA-G molecules are classical peptide presenters. PG - 305-14 AB - BACKGROUND: The physiological functions of the classical HLA (human leukocyte antigen) molecules, HLA-A, HLA-B and HLA-C, are to present peptides to T cells and to inhibit the activity of natural killer cells. In contrast, the functions of nonclassical HLA-molecules, such as HLA-E, HLA-F and HLA-G, remain to be established. The expression of HLA-G is largely limited to the placental trophoblast, where it might mediate protection of the fetus from rejection by the mother. Achieving the aim of understanding the function of HLA-G should be facilitated by information on the biochemical properties of HLA-G molecules, especially on their potential ability to act as peptide receptors. RESULTS: To study peptide presentation by HLA-G, we used stably transfected LCL721.221 cells as a source of HLA-G molecules and analysed the spectrum of extracted peptides by individual and pool sequencing. Our results indicate that HLA-G molecules, like classical HLA molecules, are associated with a wide array of peptides derived from cellular proteins. Peptides presented by HLA-G usually consisted of 9 amino acids, and adhered to a specific sequence motif, with anchor residues at position 2 (isoleucine or leucine), position 3 (proline) and the carboxy-terminal position 9 (leucine). Thus, the HLA-G peptide ligand motif follows the principles of classical HLA motifs, although it displays its own unique features. Peptide-binding assays indicated that two of the three anchor residues were sufficient for binding, and that the three natural HLA-G ligands that we identified bound, not only to HLA-G, but also to HLA-A2. This was not surprising, because the binding pockets of HLA-A2 and HLA-G overlap in their ability to recognize anchor residues at positions 2 and 9. Likewise, some, but not all, HLA-A2 peptide ligands could also bind to HLA-G. CONCLUSIONS: Nonclassical HLA-G molecules present peptides essentially in the same way as classical HLA molecules do. We determined the peptide motif that is specifically recognized by HLA-G; its basic features are described by the sequence XI/LPXXXXXL: This information should help to elucidate the physiological role of HLA-G molecules at the fetal-maternal interface. Most likely, this role is to protect fetal cells from lysis by natural killer cells, and possibly to present foreign peptides to a class of T cells that has not yet been identified. FAU - Diehl, M AU - Diehl M AD - Abteilung Tumorvirus-Immunologie (0620), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. FAU - Munz, C AU - Munz C FAU - Keilholz, W AU - Keilholz W FAU - Stevanovic, S AU - Stevanovic S FAU - Holmes, N AU - Holmes N FAU - Loke, Y W AU - Loke YW FAU - Rammensee, H G AU - Rammensee HG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Ligands) RN - 0 (Peptides) SB - IM MH - Amino Acid Sequence MH - *Antigen Presentation MH - Cell Line, Transformed MH - HLA Antigens/chemistry/genetics/*immunology MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/chemistry/genetics/*immunology MH - Humans MH - Ligands MH - Molecular Sequence Data MH - Peptides/chemistry/*immunology/isolation & purification MH - Transfection EDAT- 1996/03/01 00:00 MHDA- 1996/03/01 00:01 CRDT- 1996/03/01 00:00 PHST- 1996/03/01 00:00 [pubmed] PHST- 1996/03/01 00:01 [medline] PHST- 1996/03/01 00:00 [entrez] AID - S0960-9822(02)00481-5 [pii] AID - 10.1016/s0960-9822(02)00481-5 [doi] PST - ppublish SO - Curr Biol. 1996 Mar 1;6(3):305-14. doi: 10.1016/s0960-9822(02)00481-5.