Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach

被引：43

作者：

Stevens J. ^{[1
,2
]}

Joly E. ^{[1
,3
]}

Trowsdale J. ^{[2
]}

Butcher G.W. ^{[1
]}

机构：

[1] Lab. of Functional Immunogenetics, The Babraham Institute

[2] Department of Pathology, Division of Immunology, University of Cambridge, Cambridge CB2 1QP, Tennis Court Road

[3] UPCM, CNRS UPS 2163, CHU Purpan

来源：

BMC Immunology | / 2卷 / 1期

关键词：

Peptide; Leader Peptide; Anchor Residue; Refold Buffer; Acetonitrile Gradient;

D O I：

10.1186/1471-2172-2-5

中图分类号：

学科分类号：

摘要：

Background: Increasing evidence suggests that the effect of HLA-E on Natural Killer (NK) cell activity can be affected by the nature of the peptides bound to this non-classical, MHC class Ib molecule. However, its reduced cell surface expression, and until recently, the lack of specific monoclonal antibodies hinder studying the peptide-binding specificity HLA-E. Results: An in vitro refolding system was used to assess binding of recombinant HLA-E to either specific peptides or a nonamer random peptide library. Peptides eluted from HLA-E molecules refolded around the nonamer library were then used to determine a binding motif for HLA-E. Hydrophobic and non-charged amino acids were found to predominate along the peptide motif, with a leucine anchor at P9, but surprisingly there was no methionine preference at P2, as suggested by previous studies. Conclusions: Compared to the results obtained with rat classical class Ia MHC molecules, RT1- A1Cc and RT1-Au, HLA-E appears to refold around a random peptide library to reduced but detectable levels, suggesting that this molecule's specificity is tight but probably not as exquisite as has been previously suggested. This, and a previous report that it can associate with synthetic peptides carrying a viral sequence, suggests that HLA-E, similar to its mouse counterpart (Qa-1b), could possibly bind peptides different from MHC class I leader peptides and present them to T lymphocytes. © 2001 Stevens et al, licensee BioMed Central Ltd.

引用

共 31 条

[1]

Lee N., Llano M., Carretero M., Ishitani A., Navarro F., Lopez-Botet M., Geraghty D.E., HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A, Proc. Natl. Acad. Sci. U S A, 95, pp. 5199-5204, (1998)

[2]

Borrego F., Ulbrecht M., Weiss E.H., Coligan J.E., Brooks A.G., Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis, J. Exp. Med., 187, pp. 813-818, (1998)

[3]

Braud V.M., Allan D.S., O'Callaghan C.A., Soderstrom K., D'Andrea A., Ogg G.S., Lazetic S., Young N.T., Bell J.I., Phillips J.H., Lanier L.L., McMichael A.J., HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C, Nature, 391, pp. 795-799, (1998)

[4]

Braud V., Jones E.Y., McMichael A., The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9, Eur. J. Immunol., 27, pp. 1164-1169, (1997)

[5]

Lee N., Goodlett D.R., Ishitani A., Marquardt H., Geraghty D.E., HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences, J. Immunol., 160, pp. 4951-4960, (1998)

[6]

Braud V.M., Allan D.S., Wilson D., McMichael A.J., TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide, Curr. Biol., 8, pp. 1-10, (1998)

[7]

Tomasec P., Braud V.M., Rickards C., Powell M.B., McSharry B.P., Gadola S., Cerundolo V., Borysiewicz L.K., McMichael A.J., Wilkinson G.W., Surface expression of HLA-E, an inhibitor of natural killer cells, enhanced by human cytomegalovirus gpUL40, Science, 287, pp. 1031-1033, (2000)

[8]

O'Callaghan C.A., Tormo J., Willcox B.E., Braud V.M., Jakobsen B.K., Stuart D.I., McMichael A.J., Bell J.I., Jones E.Y., Structural features impose tight peptide binding specificity in the nonclassical MHC molecule HLA-E, Mol. Cell, 1, pp. 531-541, (1998)

[9]

Llano M., Lee N., Navarro F., Garcia P., Albar J.P., Geraghty D.E., Lopez-Botet M., HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: Preferential response to an HLA-G- derived nonamer, Eur. J. Immunol., 28, pp. 2854-2863, (1998)

[10]

Brooks A.G., Borrego F., Posch P.E., Patamawenu A., Scorzelli C.J., Ulbrecht M., Weiss E.H., Coligan J.E., Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells, J. Immunol., 162, pp. 305-313, (1999)

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